- Author:
- pmr2.import <nobody@models.cellml.org>
- Date:
- 2007-06-29 00:24:57+12:00
- Desc:
- committing version02 of huang_ferrell_1996
- Permanent Source URI:
- http://models.cellml.org/workspace/huang_ferrell_1996/rawfile/008ade5960f7a7d04e4a1a243c3f6620df79e000/huang_ferrell_1996.cellml
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<article>
<articleinfo>
<title>The Mitogen-Activated Protein Kinase (MAPK) Cascade</title>
<author>
<firstname>James</firstname>
<surname>Lawson</surname>
<affiliation>
<shortaffil>Bioengineering Institute, University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<section id="sec_status">
<title>Model Status</title>
<para>
This model has been rebuilt using the differential rate equations that Ferrel et al. use in their paper to describe the signalling pathway. Rate parameters are dimensionless, corresponding with the zero order nature of the reactions in this pathway. This zero order ultrasensitivity arises when enzymes are operating at or near saturation. The conservation equations given in the paper are unable to be implemented, as they result in an overconstrained model. This model is known to run in PCEnv.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
The mitogen-activated protein kinase (MAPK) cascade is a series of three protein kinases. Although the biological responses associated with this signalling pathway are diverse, the structure of the MAPK cascade is highly conserved between organisms (see <xref linkend="fig_pathway_diagram"/> below). The cascade relays signals from the plasma membrane to targets in the cytoplasm and nucleus, often with the affect of amplifying the signal.
</para>
<para>
This model is based on Chi-Ying Huang and James Ferrell's mathematical model of the MAPK cascade, which they describe as a series of phosphorylation and dephosphorylation reactions (1996). Ordinary differential equations (ODEs) describe sequential phosphorylation by kinases and dephosphorylation by phosphatases. The ODEs are derived from the general description of enzymatic reactions based on Michaelis-Menten kinetics.
</para>
<para>
The complete original paper reference is cited below:
</para>
<para>
<ulink url="http://www.pnas.org/cgi/content/abstract/93/19/10078">Ultrasensitivity in the mitogen-activated protein cascade</ulink>, Chi-Ying F. Huang and James E. Ferrell, Jr., 1996, <ulink url="http://www.pnas.org/">
<emphasis>Proc. Natl. Acad. Sci. USA</emphasis>
</ulink>, 93, 10078-10083. (A <ulink url="http://www.pnas.org/cgi/reprint/93/19/10078.pdf">PDF</ulink> of the article is available to subscribers on the PNAS website.) <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8816754&dopt=Abstract">PubMed ID: 8816754</ulink>
</para>
<para>
The raw CellML description of the MAPK cascade model can be downloaded in various formats as described in <xref linkend="sec_download_this_model"/>. For an example of a more complete documentation of another real reaction pathway, see <ulink url="${HTML_EXMPL_BI_EGF_INTRO}">The Bhalla Iyengar EGF Pathway Model, 1999</ulink>.
</para>
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<title>the conventional rendering of the MAPK cascade</title>
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<caption>A rendering of the MAPK cascade. Species are represented by rounded rectangles, and reactions by arrows. The action of a catalyst on a reaction is represented by dashed lines.</caption>
</informalfigure>
<para>
In CellML, models are thought of as connected networks of discrete components. These components may correspond to physiologically separated regions or chemically distinct objects, or may be useful modelling abstractions. The CellML rendering of the MAPK cascade model is shown in <xref linkend="fig_cellml_rendering"/> (the different shapes in the diagram are explained in the <ulink url="${HTML_EXMPL_GRAPHICAL_NOTATION}">notation guide</ulink>). The action of a catalyst on a reaction is represented by dashed lines.
</para>
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<caption>The CellML rendering of the MAPK cascade. The action of a catalyst on a reaction is demonstrated by dashed lines.</caption>
</informalfigure>
</sect1>
</article>
</documentation>
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<ci>k7</ci>
</apply>
<ci>K_KKPP</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="KP">
<variable units="dimensionless" public_interface="in" name="k7"/>
<variable units="micromolar" public_interface="in" name="K_KKPP"/>
<variable units="dimensionless" public_interface="in" name="a8"/>
<variable units="micromolar" public_interface="out" name="KP" initial_value="0"/>
<variable units="dimensionless" public_interface="in" name="KPase"/>
<variable units="dimensionless" public_interface="in" name="d8"/>
<variable units="micromolar" public_interface="in" name="KP_KPase"/>
<variable units="dimensionless" public_interface="in" name="a9"/>
<variable units="micromolar" public_interface="in" name="KKPP"/>
<variable units="dimensionless" public_interface="in" name="d9"/>
<variable units="micromolar" public_interface="in" name="KP_KKPP"/>
<variable units="dimensionless" public_interface="in" name="k10"/>
<variable units="micromolar" public_interface="in" name="KPP_KPase"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="KP">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>KP</ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<times/>
<ci>k7</ci>
<ci>K_KKPP</ci>
</apply>
<apply>
<times/>
<ci>a8</ci>
<ci>KP</ci>
<ci>KPase</ci>
</apply>
</apply>
<apply>
<times/>
<ci>d8</ci>
<ci>KP_KPase</ci>
</apply>
</apply>
<apply>
<times/>
<ci>a9</ci>
<ci>KP</ci>
<ci>KKPP</ci>
</apply>
</apply>
<apply>
<times/>
<ci>d9</ci>
<ci>KP_KKPP</ci>
</apply>
<apply>
<times/>
<ci>k10</ci>
<ci>KPP_KPase</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="KP_KKPP">
<variable units="second" public_interface="in" name="time"/>
<variable units="micromolar" public_interface="out" name="KP_KKPP" initial_value="0"/>
<variable units="dimensionless" public_interface="in" name="a9"/>
<variable units="micromolar" public_interface="in" name="KP"/>
<variable units="micromolar" public_interface="in" name="KKPP"/>
<variable units="dimensionless" public_interface="in" name="d9"/>
<variable units="dimensionless" public_interface="in" name="k9"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="KP_KKPP">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>KP_KKPP</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>a9</ci>
<ci>KP</ci>
<ci>KKPP</ci>
</apply>
<apply>
<times/>
<apply>
<plus/>
<ci>d9</ci>
<ci>k9</ci>
</apply>
<ci>KP_KKPP</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="KP_KPase">
<variable units="micromolar" public_interface="out" name="KP_KPase" initial_value="0"/>
<variable units="dimensionless" public_interface="in" name="a8"/>
<variable units="micromolar" public_interface="in" name="KP"/>
<variable units="micromolar" public_interface="in" name="KPase"/>
<variable units="dimensionless" public_interface="in" name="d8"/>
<variable units="dimensionless" public_interface="in" name="k8"/>
<variable units="micromolar" public_interface="in" name="KP_KKPP"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="KP_KPase">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>KP_KPase</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>a8</ci>
<ci>KP</ci>
<ci>KPase</ci>
</apply>
<apply>
<times/>
<apply>
<plus/>
<ci>d8</ci>
<ci>k8</ci>
</apply>
<ci>KP_KPase</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="KPP">
<variable units="dimensionless" public_interface="in" name="a10"/>
<variable units="micromolar" public_interface="out" name="KPP" initial_value="0"/>
<variable units="micromolar" public_interface="in" name="KPase"/>
<variable units="dimensionless" public_interface="in" name="d10"/>
<variable units="micromolar" public_interface="in" name="KPP_KPase"/>
<variable units="dimensionless" public_interface="in" name="k9"/>
<variable units="micromolar" public_interface="in" name="KP_KKPP"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="KPP">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>KPP</ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<apply>
<minus/>
<ci>a10</ci>
</apply>
<ci>KPP</ci>
<ci>KPase</ci>
</apply>
<apply>
<times/>
<ci>d10</ci>
<ci>KPP_KPase</ci>
</apply>
<apply>
<times/>
<ci>k9</ci>
<ci>KP_KKPP</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="KPP_KPase">
<variable units="dimensionless" public_interface="in" name="a10"/>
<variable units="micromolar" public_interface="in" name="KPP"/>
<variable units="micromolar" public_interface="in" name="KPase"/>
<variable units="dimensionless" public_interface="in" name="d10"/>
<variable units="dimensionless" public_interface="in" name="k10"/>
<variable units="micromolar" public_interface="out" name="KPP_KPase" initial_value="0"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="KPP_KPase">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>KPP_KPase</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>a10</ci>
<ci>KPP</ci>
<ci>KPase</ci>
</apply>
<apply>
<times/>
<apply>
<plus/>
<ci>d10</ci>
<ci>k10</ci>
</apply>
<ci>KPP_KPase</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="rate_constants">
<variable units="dimensionless" public_interface="out" name="a1" initial_value="1000"/>
<variable units="dimensionless" public_interface="out" name="a2" initial_value="1000"/>
<variable units="dimensionless" public_interface="out" name="a3" initial_value="1000"/>
<variable units="dimensionless" public_interface="out" name="a4" initial_value="1000"/>
<variable units="dimensionless" public_interface="out" name="a5" initial_value="1000"/>
<variable units="dimensionless" public_interface="out" name="a6" initial_value="1000"/>
<variable units="dimensionless" public_interface="out" name="a7" initial_value="1000"/>
<variable units="dimensionless" public_interface="out" name="a8" initial_value="1000"/>
<variable units="dimensionless" public_interface="out" name="a9" initial_value="1000"/>
<variable units="dimensionless" public_interface="out" name="a10" initial_value="1000"/>
<variable units="dimensionless" public_interface="out" name="d1" initial_value="150"/>
<variable units="dimensionless" public_interface="out" name="d2" initial_value="150"/>
<variable units="dimensionless" public_interface="out" name="d3" initial_value="150"/>
<variable units="dimensionless" public_interface="out" name="d4" initial_value="150"/>
<variable units="dimensionless" public_interface="out" name="d5" initial_value="150"/>
<variable units="dimensionless" public_interface="out" name="d6" initial_value="150"/>
<variable units="dimensionless" public_interface="out" name="d7" initial_value="150"/>
<variable units="dimensionless" public_interface="out" name="d8" initial_value="150"/>
<variable units="dimensionless" public_interface="out" name="d9" initial_value="150"/>
<variable units="dimensionless" public_interface="out" name="d10" initial_value="150"/>
<variable units="dimensionless" public_interface="out" name="k1" initial_value="150"/>
<variable units="dimensionless" public_interface="out" name="k2" initial_value="150"/>
<variable units="dimensionless" public_interface="out" name="k3" initial_value="150"/>
<variable units="dimensionless" public_interface="out" name="k4" initial_value="150"/>
<variable units="dimensionless" public_interface="out" name="k5" initial_value="150"/>
<variable units="dimensionless" public_interface="out" name="k6" initial_value="150"/>
<variable units="dimensionless" public_interface="out" name="k7" initial_value="150"/>
<variable units="dimensionless" public_interface="out" name="k8" initial_value="150"/>
<variable units="dimensionless" public_interface="out" name="k9" initial_value="150"/>
<variable units="dimensionless" public_interface="out" name="k10" initial_value="150"/>
</component>
<component name="E1">
<variable units="micromolar" public_interface="out" name="E1" initial_value="0.00003"/>
<variable units="micromolar" public_interface="in" name="KKK_E1"/>
<variable units="micromolar" public_interface="in" name="KKK"/>
<variable units="dimensionless" public_interface="in" name="a1"/>
<variable units="dimensionless" public_interface="in" name="d1"/>
<variable units="dimensionless" public_interface="in" name="k2"/>
<variable units="micromolar" public_interface="in" name="KKKstar_E2"/>
<variable units="dimensionless" public_interface="in" name="k1"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="E1">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>E1</ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<apply>
<minus/>
<ci>a1</ci>
</apply>
<ci>KKK</ci>
<ci>E1</ci>
</apply>
<apply>
<times/>
<ci>d1</ci>
<ci>KKK_E1</ci>
</apply>
<apply>
<times/>
<ci>k2</ci>
<ci>KKKstar_E2</ci>
</apply>
</apply>
<apply>
<times/>
<ci>a1</ci>
<ci>KKK</ci>
<ci>E1</ci>
</apply>
</apply>
<apply>
<times/>
<ci>KKK_E1</ci>
<apply>
<plus/>
<ci>d1</ci>
<ci>k1</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="E2">
<variable units="micromolar" public_interface="out" name="E2" initial_value="0.0003"/>
<variable units="micromolar" public_interface="in" name="KKKstar"/>
<variable units="dimensionless" public_interface="in" name="a2"/>
<variable units="dimensionless" public_interface="in" name="d2"/>
<variable units="micromolar" public_interface="in" name="KKKstar_E2"/>
<variable units="dimensionless" public_interface="in" name="k1"/>
<variable units="micromolar" public_interface="in" name="KKK_E1"/>
<variable units="dimensionless" public_interface="in" name="k3"/>
<variable units="dimensionless" public_interface="in" name="d3"/>
<variable units="micromolar" public_interface="in" name="KK_KKKstar"/>
<variable units="dimensionless" public_interface="in" name="a3"/>
<variable units="micromolar" public_interface="in" name="KK"/>
<variable units="dimensionless" public_interface="in" name="k5"/>
<variable units="dimensionless" public_interface="in" name="d5"/>
<variable units="micromolar" public_interface="in" name="KKP_KKKstar"/>
<variable units="dimensionless" public_interface="in" name="a5"/>
<variable units="micromolar" public_interface="in" name="KKP"/>
<variable units="dimensionless" public_interface="in" name="k2"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="E2">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>E2</ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<apply>
<minus/>
<ci>a2</ci>
</apply>
<ci>KKKstar</ci>
<ci>E2</ci>
</apply>
<apply>
<times/>
<ci>d2</ci>
<ci>KKKstar_E2</ci>
</apply>
<apply>
<times/>
<ci>k1</ci>
<ci>KKK_E1</ci>
</apply>
<apply>
<times/>
<apply>
<plus/>
<ci>k3</ci>
<ci>d3</ci>
</apply>
<ci>KK_KKKstar</ci>
</apply>
</apply>
<apply>
<times/>
<ci>a3</ci>
<ci>KKKstar</ci>
<ci>KK</ci>
</apply>
</apply>
<apply>
<times/>
<apply>
<plus/>
<ci>k5</ci>
<ci>d5</ci>
</apply>
<ci>KKP_KKKstar</ci>
</apply>
</apply>
<apply>
<times/>
<ci>a5</ci>
<ci>KKP</ci>
<ci>KKKstar</ci>
</apply>
</apply>
<apply>
<times/>
<ci>a2</ci>
<ci>KKKstar</ci>
<ci>E2</ci>
</apply>
</apply>
<apply>
<times/>
<apply>
<plus/>
<ci>d2</ci>
<ci>k2</ci>
</apply>
<ci>KKKstar_E2</ci>
</apply>
</apply>
</apply>
</math>
</component>
<connection>
<map_components component_2="K" component_1="environment"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="KKK" component_1="environment"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="KKK" component_1="environment"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="KKK_E1" component_1="environment"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="KKKstar" component_1="environment"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="KKKstar_E2" component_1="environment"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="KK" component_1="environment"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="KK_KKKstar" component_1="environment"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="KKP" component_1="environment"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="KKP_KKPase" component_1="environment"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="KKP_KKKstar" component_1="environment"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="KKPP" component_1="environment"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="KKPP_KKPase" component_1="environment"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="K_KKPP" component_1="environment"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="KP" component_1="environment"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="KP_KKPP" component_1="environment"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="KP_KPase" component_1="environment"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="KPP" component_1="environment"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="KPP_KPase" component_1="environment"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="E1" component_1="environment"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="E2" component_1="environment"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="K" component_1="rate_constants"/>
<map_variables variable_2="a7" variable_1="a7"/>
<map_variables variable_2="d7" variable_1="d7"/>
<map_variables variable_2="k8" variable_1="k8"/>
</connection>
<connection>
<map_components component_2="K" component_1="KKPP"/>
<map_variables variable_2="KKPP" variable_1="KKPP"/>
</connection>
<connection>
<map_components component_2="K" component_1="K_KKPP"/>
<map_variables variable_2="K_KKPP" variable_1="K_KKPP"/>
</connection>
<connection>
<map_components component_2="K" component_1="KP_KPase"/>
<map_variables variable_2="KP_KPase" variable_1="KP_KPase"/>
</connection>
<connection>
<map_components component_2="KKK" component_1="rate_constants"/>
<map_variables variable_2="a1" variable_1="a1"/>
<map_variables variable_2="d1" variable_1="d1"/>
<map_variables variable_2="k2" variable_1="k2"/>
</connection>
<connection>
<map_components component_2="KKK" component_1="E1"/>
<map_variables variable_2="E1" variable_1="E1"/>
</connection>
<connection>
<map_components component_2="KKK" component_1="KKK_E1"/>
<map_variables variable_2="KKK_E1" variable_1="KKK_E1"/>
</connection>
<connection>
<map_components component_2="KKK" component_1="KKKstar_E2"/>
<map_variables variable_2="KKKstar_E2" variable_1="KKKstar_E2"/>
</connection>
<connection>
<map_components component_2="KKK_E1" component_1="rate_constants"/>
<map_variables variable_2="a1" variable_1="a1"/>
<map_variables variable_2="d1" variable_1="d1"/>
<map_variables variable_2="k1" variable_1="k1"/>
</connection>
<connection>
<map_components component_2="KKK_E1" component_1="KKK"/>
<map_variables variable_2="KKK" variable_1="KKK"/>
</connection>
<connection>
<map_components component_2="KKK_E1" component_1="E1"/>
<map_variables variable_2="E1" variable_1="E1"/>
</connection>
<connection>
<map_components component_2="KKKstar" component_1="rate_constants"/>
<map_variables variable_2="a2" variable_1="a2"/>
<map_variables variable_2="a3" variable_1="a3"/>
<map_variables variable_2="a5" variable_1="a5"/>
<map_variables variable_2="d2" variable_1="d2"/>
<map_variables variable_2="d3" variable_1="d3"/>
<map_variables variable_2="d5" variable_1="d5"/>
<map_variables variable_2="k1" variable_1="k1"/>
<map_variables variable_2="k3" variable_1="k3"/>
<map_variables variable_2="k5" variable_1="k5"/>
</connection>
<connection>
<map_components component_2="KKKstar" component_1="E2"/>
<map_variables variable_2="E2" variable_1="E2"/>
</connection>
<connection>
<map_components component_2="KKKstar" component_1="KKKstar_E2"/>
<map_variables variable_2="KKKstar_E2" variable_1="KKKstar_E2"/>
</connection>
<connection>
<map_components component_2="KKKstar" component_1="KKK_E1"/>
<map_variables variable_2="KKK_E1" variable_1="KKK_E1"/>
</connection>
<connection>
<map_components component_2="KKKstar" component_1="KK_KKKstar"/>
<map_variables variable_2="KK_KKKstar" variable_1="KK_KKKstar"/>
</connection>
<connection>
<map_components component_2="KKKstar" component_1="KK"/>
<map_variables variable_2="KK" variable_1="KK"/>
</connection>
<connection>
<map_components component_2="KKKstar" component_1="KKP_KKKstar"/>
<map_variables variable_2="KKP_KKKstar" variable_1="KKP_KKKstar"/>
</connection>
<connection>
<map_components component_2="KKKstar" component_1="KKP"/>
<map_variables variable_2="KKP" variable_1="KKP"/>
</connection>
<connection>
<map_components component_2="KKKstar_E2" component_1="rate_constants"/>
<map_variables variable_2="a2" variable_1="a2"/>
<map_variables variable_2="d2" variable_1="d2"/>
<map_variables variable_2="k2" variable_1="k2"/>
</connection>
<connection>
<map_components component_2="KKKstar_E2" component_1="KKKstar"/>
<map_variables variable_2="KKKstar" variable_1="KKKstar"/>
</connection>
<connection>
<map_components component_2="KKKstar_E2" component_1="E2"/>
<map_variables variable_2="E2" variable_1="E2"/>
</connection>
<connection>
<map_components component_2="KK" component_1="rate_constants"/>
<map_variables variable_2="a3" variable_1="a3"/>
<map_variables variable_2="d3" variable_1="d3"/>
<map_variables variable_2="k4" variable_1="k4"/>
</connection>
<connection>
<map_components component_2="KK" component_1="KKKstar"/>
<map_variables variable_2="KKKstar" variable_1="KKKstar"/>
</connection>
<connection>
<map_components component_2="KK" component_1="KK_KKKstar"/>
<map_variables variable_2="KK_KKKstar" variable_1="KK_KKKstar"/>
</connection>
<connection>
<map_components component_2="KK" component_1="KKP_KKPase"/>
<map_variables variable_2="KKP_KKPase" variable_1="KKP_KKPase"/>
</connection>
<connection>
<map_components component_2="KK_KKKstar" component_1="rate_constants"/>
<map_variables variable_2="a3" variable_1="a3"/>
<map_variables variable_2="d3" variable_1="d3"/>
<map_variables variable_2="k3" variable_1="k3"/>
</connection>
<connection>
<map_components component_2="KK_KKKstar" component_1="KK"/>
<map_variables variable_2="KK" variable_1="KK"/>
</connection>
<connection>
<map_components component_2="KK_KKKstar" component_1="KKKstar"/>
<map_variables variable_2="KKKstar" variable_1="KKKstar"/>
</connection>
<connection>
<map_components component_2="KKP" component_1="rate_constants"/>
<map_variables variable_2="a4" variable_1="a4"/>
<map_variables variable_2="a5" variable_1="a5"/>
<map_variables variable_2="d4" variable_1="d4"/>
<map_variables variable_2="d5" variable_1="d5"/>
<map_variables variable_2="k3" variable_1="k3"/>
<map_variables variable_2="k6" variable_1="k6"/>
</connection>
<connection>
<map_components component_2="KKP" component_1="KKPase"/>
<map_variables variable_2="KKPase" variable_1="KKPase"/>
</connection>
<connection>
<map_components component_2="KKP" component_1="KKP_KKPase"/>
<map_variables variable_2="KKP_KKPase" variable_1="KKP_KKPase"/>
</connection>
<connection>
<map_components component_2="KKP" component_1="KK_KKKstar"/>
<map_variables variable_2="KK_KKKstar" variable_1="KK_KKKstar"/>
</connection>
<connection>
<map_components component_2="KKP" component_1="KKPP_KKPase"/>
<map_variables variable_2="KKPP_KKPase" variable_1="KKPP_KKPase"/>
</connection>
<connection>
<map_components component_2="KKP" component_1="KKP_KKKstar"/>
<map_variables variable_2="KKP_KKKstar" variable_1="KKP_KKKstar"/>
</connection>
<connection>
<map_components component_2="KKP" component_1="KKKstar"/>
<map_variables variable_2="KKKstar" variable_1="KKKstar"/>
</connection>
<component name="KPase">
<variable units="second" public_interface="in" name="time"/>
<variable units="micromolar" public_interface="out" name="KPase" initial_value="0.12"/>
<variable units="dimensionless" public_interface="in" name="a8"/>
<variable units="dimensionless" public_interface="in" name="a10"/>
<variable units="dimensionless" public_interface="in" name="d8"/>
<variable units="dimensionless" public_interface="in" name="d10"/>
<variable units="dimensionless" public_interface="in" name="k8"/>
<variable units="dimensionless" public_interface="in" name="k10"/>
<variable units="micromolar" public_interface="in" name="KP"/>
<variable units="micromolar" public_interface="in" name="KP_KPase"/>
<variable units="micromolar" public_interface="in" name="KPP"/>
<variable units="micromolar" public_interface="in" name="KPP_KPase"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="KPase">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>KPase</ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<apply>
<minus/>
<ci>a8</ci>
</apply>
<ci>KP</ci>
<ci>KPase</ci>
</apply>
<apply>
<times/>
<apply>
<plus/>
<ci>d8</ci>
<ci>k8</ci>
</apply>
<ci>KP_KPase</ci>
</apply>
</apply>
<apply>
<times/>
<ci>a10</ci>
<ci>KPP</ci>
<ci>KPase</ci>
</apply>
</apply>
<apply>
<times/>
<apply>
<plus/>
<ci>d10</ci>
<ci>k10</ci>
</apply>
<ci>KPP_KPase</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="KKPase">
<variable units="second" public_interface="in" name="time"/>
<variable units="micromolar" public_interface="out" name="KKPase" initial_value="0.0003"/>
<variable units="dimensionless" public_interface="in" name="a4"/>
<variable units="dimensionless" public_interface="in" name="a6"/>
<variable units="dimensionless" public_interface="in" name="d4"/>
<variable units="dimensionless" public_interface="in" name="d6"/>
<variable units="dimensionless" public_interface="in" name="k4"/>
<variable units="dimensionless" public_interface="in" name="k6"/>
<variable units="micromolar" public_interface="in" name="KKP"/>
<variable units="micromolar" public_interface="in" name="KKPP"/>
<variable units="micromolar" public_interface="in" name="KKP_KKPase"/>
<variable units="micromolar" public_interface="in" name="KKPP_KKPase"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="KKPase">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>KKPase</ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<apply>
<minus/>
<ci>a4</ci>
</apply>
<ci>KKP</ci>
<ci>KKPase</ci>
</apply>
<apply>
<times/>
<apply>
<plus/>
<ci>d4</ci>
<ci>k4</ci>
</apply>
<ci>KKP_KKPase</ci>
</apply>
</apply>
<apply>
<times/>
<ci>a6</ci>
<ci>KKPP</ci>
<ci>KKPase</ci>
</apply>
</apply>
<apply>
<times/>
<apply>
<plus/>
<ci>d6</ci>
<ci>k6</ci>
</apply>
<ci>KKPP_KKPase</ci>
</apply>
</apply>
</apply>
</math>
</component>
<connection>
<map_components component_2="KKP_KKPase" component_1="rate_constants"/>
<map_variables variable_2="a4" variable_1="a4"/>
<map_variables variable_2="d4" variable_1="d4"/>
<map_variables variable_2="k4" variable_1="k4"/>
</connection>
<connection>
<map_components component_2="KKP_KKPase" component_1="KKP"/>
<map_variables variable_2="KKP" variable_1="KKP"/>
</connection>
<connection>
<map_components component_2="KKP_KKPase" component_1="KKPase"/>
<map_variables variable_2="KKPase" variable_1="KKPase"/>
</connection>
<connection>
<map_components component_2="KKP_KKKstar" component_1="rate_constants"/>
<map_variables variable_2="a5" variable_1="a5"/>
<map_variables variable_2="d5" variable_1="d5"/>
<map_variables variable_2="k5" variable_1="k5"/>
</connection>
<connection>
<map_components component_2="KKP_KKKstar" component_1="KKP"/>
<map_variables variable_2="KKP" variable_1="KKP"/>
</connection>
<connection>
<map_components component_2="KKP_KKKstar" component_1="KKKstar"/>
<map_variables variable_2="KKKstar" variable_1="KKKstar"/>
</connection>
<connection>
<map_components component_2="KKPP" component_1="rate_constants"/>
<map_variables variable_2="a6" variable_1="a6"/>
<map_variables variable_2="a7" variable_1="a7"/>
<map_variables variable_2="a9" variable_1="a9"/>
<map_variables variable_2="d6" variable_1="d6"/>
<map_variables variable_2="d7" variable_1="d7"/>
<map_variables variable_2="d9" variable_1="d9"/>
<map_variables variable_2="k5" variable_1="k5"/>
<map_variables variable_2="k7" variable_1="k7"/>
<map_variables variable_2="k9" variable_1="k9"/>
</connection>
<connection>
<map_components component_2="KKPP" component_1="KKP_KKKstar"/>
<map_variables variable_2="KKP_KKKstar" variable_1="KKP_KKKstar"/>
</connection>
<connection>
<map_components component_2="KKPP" component_1="KKPase"/>
<map_variables variable_2="KKPase" variable_1="KKPase"/>
</connection>
<connection>
<map_components component_2="KKPP" component_1="KKPP_KKPase"/>
<map_variables variable_2="KKPP_KKPase" variable_1="KKPP_KKPase"/>
</connection>
<connection>
<map_components component_2="KKPP" component_1="K"/>
<map_variables variable_2="K" variable_1="K"/>
</connection>
<connection>
<map_components component_2="KKPP" component_1="K_KKPP"/>
<map_variables variable_2="K_KKPP" variable_1="K_KKPP"/>
</connection>
<connection>
<map_components component_2="KKPP" component_1="KP_KKPP"/>
<map_variables variable_2="KP_KKPP" variable_1="KP_KKPP"/>
</connection>
<connection>
<map_components component_2="KKPP" component_1="KP"/>
<map_variables variable_2="KP" variable_1="KP"/>
</connection>
<connection>
<map_components component_2="KKPP_KKPase" component_1="rate_constants"/>
<map_variables variable_2="a6" variable_1="a6"/>
<map_variables variable_2="d6" variable_1="d6"/>
<map_variables variable_2="k6" variable_1="k6"/>
</connection>
<connection>
<map_components component_2="KKPP_KKPase" component_1="KKPP"/>
<map_variables variable_2="KKPP" variable_1="KKPP"/>
</connection>
<connection>
<map_components component_2="KKPP_KKPase" component_1="KKPase"/>
<map_variables variable_2="KKPase" variable_1="KKPase"/>
</connection>
<connection>
<map_components component_2="K_KKPP" component_1="rate_constants"/>
<map_variables variable_2="a7" variable_1="a7"/>
<map_variables variable_2="d7" variable_1="d7"/>
<map_variables variable_2="k7" variable_1="k7"/>
</connection>
<connection>
<map_components component_2="K_KKPP" component_1="K"/>
<map_variables variable_2="K" variable_1="K"/>
</connection>
<connection>
<map_components component_2="K_KKPP" component_1="KKPP"/>
<map_variables variable_2="KKPP" variable_1="KKPP"/>
</connection>
<connection>
<map_components component_2="KP" component_1="rate_constants"/>
<map_variables variable_2="a8" variable_1="a8"/>
<map_variables variable_2="a9" variable_1="a9"/>
<map_variables variable_2="d8" variable_1="d8"/>
<map_variables variable_2="d9" variable_1="d9"/>
<map_variables variable_2="k7" variable_1="k7"/>
<map_variables variable_2="k10" variable_1="k10"/>
</connection>
<connection>
<map_components component_2="KP" component_1="K_KKPP"/>
<map_variables variable_2="K_KKPP" variable_1="K_KKPP"/>
</connection>
<connection>
<map_components component_2="KP" component_1="KPase"/>
<map_variables variable_2="KPase" variable_1="KPase"/>
</connection>
<connection>
<map_components component_2="KP" component_1="KP_KPase"/>
<map_variables variable_2="KP_KPase" variable_1="KP_KPase"/>
</connection>
<connection>
<map_components component_2="KP" component_1="KKPP"/>
<map_variables variable_2="KKPP" variable_1="KKPP"/>
</connection>
<connection>
<map_components component_2="KP" component_1="KP_KKPP"/>
<map_variables variable_2="KP_KKPP" variable_1="KP_KKPP"/>
</connection>
<connection>
<map_components component_2="KP" component_1="KPP_KPase"/>
<map_variables variable_2="KPP_KPase" variable_1="KPP_KPase"/>
</connection>
<connection>
<map_components component_2="KP_KKPP" component_1="rate_constants"/>
<map_variables variable_2="a9" variable_1="a9"/>
<map_variables variable_2="d9" variable_1="d9"/>
<map_variables variable_2="k9" variable_1="k9"/>
</connection>
<connection>
<map_components component_2="KP_KKPP" component_1="KP"/>
<map_variables variable_2="KP" variable_1="KP"/>
</connection>
<connection>
<map_components component_2="KP_KKPP" component_1="KKPP"/>
<map_variables variable_2="KKPP" variable_1="KKPP"/>
</connection>
<connection>
<map_components component_2="KP_KPase" component_1="rate_constants"/>
<map_variables variable_2="a8" variable_1="a8"/>
<map_variables variable_2="d8" variable_1="d8"/>
<map_variables variable_2="k8" variable_1="k8"/>
</connection>
<connection>
<map_components component_2="KP_KPase" component_1="KP"/>
<map_variables variable_2="KP" variable_1="KP"/>
</connection>
<connection>
<map_components component_2="KP_KPase" component_1="KPase"/>
<map_variables variable_2="KPase" variable_1="KPase"/>
</connection>
<connection>
<map_components component_2="KP_KPase" component_1="KP_KKPP"/>
<map_variables variable_2="KP_KKPP" variable_1="KP_KKPP"/>
</connection>
<connection>
<map_components component_2="KPP" component_1="rate_constants"/>
<map_variables variable_2="a10" variable_1="a10"/>
<map_variables variable_2="d10" variable_1="d10"/>
<map_variables variable_2="k9" variable_1="k9"/>
</connection>
<connection>
<map_components component_2="KPP" component_1="KPase"/>
<map_variables variable_2="KPase" variable_1="KPase"/>
</connection>
<connection>
<map_components component_2="KPP" component_1="KPP_KPase"/>
<map_variables variable_2="KPP_KPase" variable_1="KPP_KPase"/>
</connection>
<connection>
<map_components component_2="KPP" component_1="KP_KKPP"/>
<map_variables variable_2="KP_KKPP" variable_1="KP_KKPP"/>
</connection>
<connection>
<map_components component_2="KPP_KPase" component_1="rate_constants"/>
<map_variables variable_2="a10" variable_1="a10"/>
<map_variables variable_2="d10" variable_1="d10"/>
<map_variables variable_2="k10" variable_1="k10"/>
</connection>
<connection>
<map_components component_2="KPP_KPase" component_1="KPP"/>
<map_variables variable_2="KPP" variable_1="KPP"/>
</connection>
<connection>
<map_components component_2="KPP_KPase" component_1="KPase"/>
<map_variables variable_2="KPase" variable_1="KPase"/>
</connection>
<connection>
<map_components component_2="E1" component_1="rate_constants"/>
<map_variables variable_2="a1" variable_1="a1"/>
<map_variables variable_2="d1" variable_1="d1"/>
<map_variables variable_2="k1" variable_1="k1"/>
<map_variables variable_2="k2" variable_1="k2"/>
</connection>
<connection>
<map_components component_2="E1" component_1="KKK_E1"/>
<map_variables variable_2="KKK_E1" variable_1="KKK_E1"/>
</connection>
<connection>
<map_components component_2="E1" component_1="KKK"/>
<map_variables variable_2="KKK" variable_1="KKK"/>
</connection>
<connection>
<map_components component_2="E1" component_1="KKKstar_E2"/>
<map_variables variable_2="KKKstar_E2" variable_1="KKKstar_E2"/>
</connection>
<connection>
<map_components component_2="E2" component_1="rate_constants"/>
<map_variables variable_2="a2" variable_1="a2"/>
<map_variables variable_2="a3" variable_1="a3"/>
<map_variables variable_2="a5" variable_1="a5"/>
<map_variables variable_2="d2" variable_1="d2"/>
<map_variables variable_2="d3" variable_1="d3"/>
<map_variables variable_2="d5" variable_1="d5"/>
<map_variables variable_2="k1" variable_1="k1"/>
<map_variables variable_2="k2" variable_1="k2"/>
<map_variables variable_2="k3" variable_1="k3"/>
<map_variables variable_2="k5" variable_1="k5"/>
</connection>
<connection>
<map_components component_2="E2" component_1="KKKstar"/>
<map_variables variable_2="KKKstar" variable_1="KKKstar"/>
</connection>
<connection>
<map_components component_2="E2" component_1="KKKstar_E2"/>
<map_variables variable_2="KKKstar_E2" variable_1="KKKstar_E2"/>
</connection>
<connection>
<map_components component_2="E2" component_1="KKK_E1"/>
<map_variables variable_2="KKK_E1" variable_1="KKK_E1"/>
</connection>
<connection>
<map_components component_2="E2" component_1="KK_KKKstar"/>
<map_variables variable_2="KK_KKKstar" variable_1="KK_KKKstar"/>
</connection>
<connection>
<map_components component_2="E2" component_1="KK"/>
<map_variables variable_2="KK" variable_1="KK"/>
</connection>
<connection>
<map_components component_2="E2" component_1="KKP_KKKstar"/>
<map_variables variable_2="KKP_KKKstar" variable_1="KKP_KKKstar"/>
</connection>
<connection>
<map_components component_2="E2" component_1="KKP"/>
<map_variables variable_2="KKP" variable_1="KKP"/>
</connection>
<connection>
<map_components component_2="KPase" component_1="environment"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="KPase" component_1="rate_constants"/>
<map_variables variable_2="a8" variable_1="a8"/>
<map_variables variable_2="a10" variable_1="a10"/>
<map_variables variable_2="d8" variable_1="d8"/>
<map_variables variable_2="d10" variable_1="d10"/>
<map_variables variable_2="k8" variable_1="k8"/>
<map_variables variable_2="k10" variable_1="k10"/>
</connection>
<connection>
<map_components component_2="KPase" component_1="KP"/>
<map_variables variable_2="KP" variable_1="KP"/>
</connection>
<connection>
<map_components component_2="KPase" component_1="KP_KPase"/>
<map_variables variable_2="KP_KPase" variable_1="KP_KPase"/>
</connection>
<connection>
<map_components component_2="KPase" component_1="KPP"/>
<map_variables variable_2="KPP" variable_1="KPP"/>
</connection>
<connection>
<map_components component_2="KPase" component_1="KPP_KPase"/>
<map_variables variable_2="KPP_KPase" variable_1="KPP_KPase"/>
</connection>
<connection>
<map_components component_2="KKPase" component_1="environment"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="KKPase" component_1="rate_constants"/>
<map_variables variable_2="a4" variable_1="a4"/>
<map_variables variable_2="a6" variable_1="a6"/>
<map_variables variable_2="d4" variable_1="d4"/>
<map_variables variable_2="d6" variable_1="d6"/>
<map_variables variable_2="k4" variable_1="k4"/>
<map_variables variable_2="k6" variable_1="k6"/>
</connection>
<connection>
<map_components component_2="KKPase" component_1="KKP"/>
<map_variables variable_2="KKP" variable_1="KKP"/>
</connection>
<connection>
<map_components component_2="KKPase" component_1="KKPP"/>
<map_variables variable_2="KKPP" variable_1="KKPP"/>
</connection>
<connection>
<map_components component_2="KKPase" component_1="KKP_KKPase"/>
<map_variables variable_2="KKP_KKPase" variable_1="KKP_KKPase"/>
</connection>
<connection>
<map_components component_2="KKPase" component_1="KKPP_KKPase"/>
<map_variables variable_2="KKPP_KKPase" variable_1="KKPP_KKPase"/>
</connection>
<rdf:RDF>
<rdf:Bag rdf:about="rdf:#eba8c7ef-3b79-452e-b009-7d341b82f7ee">
<rdf:li>Oocyte</rdf:li>
<rdf:li>signal transduction</rdf:li>
</rdf:Bag>
<rdf:Seq rdf:about="rdf:#258e0e86-8090-423d-9d46-9e2100b326e6">
<rdf:li rdf:resource="rdf:#1a5d8c3e-2fb2-4889-bc54-42edf4701f73"/>
<rdf:li rdf:resource="rdf:#d8d17dd3-09e1-444f-ab40-d271cccb6858"/>
</rdf:Seq>
<rdf:Description rdf:about="rdf:#8684e245-1046-4085-a60e-53e843649852">
<vCard:Given>Autumn</vCard:Given>
<vCard:Family>Cuellar</vCard:Family>
<vCard:Other>A.</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#c5c42e8c-4142-4672-a3a6-6760517ed8c2">
<dcterms:W3CDTF>2002-01-22</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="rdf:#9b385d0c-3d5f-4e08-8571-73486e37e88e">
<dcterms:W3CDTF>2002-07-22</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="#MAPKK">
<dcterms:alternative>
mitogen-activated protein kinase kinase
</dcterms:alternative>
<dcterms:alternative>MAPK kinase</dcterms:alternative>
<dc:title>MAPKK</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#25fdae06-6914-4c4a-aaa0-58387f5b5675">
<vCard:Given>James</vCard:Given>
<vCard:Family>Lawson</vCard:Family>
<vCard:Other>Richard</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#6a7f76db-b28a-464e-9bee-3d44c752b950">
<vCard:N rdf:resource="rdf:#1a71e812-46dc-4577-becd-4a0b40a13023"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#e701e488-0c43-4e11-a40e-9ed70e525e92">
<vCard:N rdf:resource="rdf:#25fdae06-6914-4c4a-aaa0-58387f5b5675"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#f8e4f07e-c305-4f2a-a533-320df9bb3cb7">
<dcterms:modified rdf:resource="rdf:#e81f7e5a-6a90-46b2-8bcd-9f1a3f641416"/>
<rdf:value>
Added publication date information.
</rdf:value>
<cmeta:modifier rdf:resource="rdf:#0cacbd05-787b-42d2-800d-b363ae69c418"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#00ecd585-e3f7-425f-8896-da6bef3d1148">
<dc:creator rdf:resource="rdf:#6b2c856e-4073-4777-91c5-5b0288057ff1"/>
<rdf:value>This is the CellML description of Huang and Ferrell's mathematical
model of the mitogen-activated protein kinase (MAPK) cascade (1996).
This signalling pathway involves a series of three, highly conserved
protein kinases which are associated with a diverse array of
biological responses.</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="rdf:#b4f1922b-4a2b-493c-af27-032f443d06bd">
<vCard:N rdf:resource="rdf:#db5c992f-914b-4919-9f36-dcf0c6867980"/>
</rdf:Description>
<rdf:Description rdf:about="#MAPKKK_">
<dcterms:alternative>
activated mitogen-activated protein kinase kinase kinase
</dcterms:alternative>
<dcterms:alternative>activated MAPK kinase kinase</dcterms:alternative>
<dcterms:alternative>activated MAPKKK</dcterms:alternative>
<dc:title>MAPKKK_</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#34308850-7653-4d14-9548-31c3f4c7921b">
<vCard:ORG rdf:resource="rdf:#a83a271f-0437-460a-a1d9-559066d90267"/>
<vCard:EMAIL rdf:resource="rdf:#329ae480-a36a-446b-9d47-e784a5e1a2f1"/>
<vCard:N rdf:resource="rdf:#9282263c-2e0f-440f-b006-9e5775e940c1"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#db5c992f-914b-4919-9f36-dcf0c6867980">
<vCard:Given>Catherine</vCard:Given>
<vCard:Family>Lloyd</vCard:Family>
<vCard:Other>May</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#fb205912-9a0a-4eea-a124-144f0030d8da">
<dcterms:W3CDTF>1996-09-17</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="#MAPKKK">
<dcterms:alternative>
mitogen-activated protein kinase kinase kinase
</dcterms:alternative>
<dcterms:alternative>MAPK kinase kinase</dcterms:alternative>
<dc:title>MAPKKK</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#c4926013-b136-4f61-a838-e376f4323400">
<dcterms:W3CDTF>2001-10-24</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="rdf:#6b2c856e-4073-4777-91c5-5b0288057ff1">
<vCard:FN>Catherine Lloyd</vCard:FN>
</rdf:Description>
<rdf:Description rdf:about="#MAPK_P_ase">
<dcterms:alternative>
mitogen-activated protein kinase phosphatase
</dcterms:alternative>
<dc:title>MAPK_P_ase</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#0cacbd05-787b-42d2-800d-b363ae69c418">
<vCard:N rdf:resource="rdf:#8d7429c8-8597-4fc4-ab13-263e0c146f13"/>
</rdf:Description>
<rdf:Description rdf:about="#MAPK_PP">
<dcterms:alternative>
doubly phosphorylated mitogen-activated protein kinase
</dcterms:alternative>
<dc:title>MAPK_PP</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#5be2f7ea-6223-4da2-a013-5daebcd9d2c8">
<vCard:N rdf:resource="rdf:#8684e245-1046-4085-a60e-53e843649852"/>
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<rdf:Description rdf:about="rdf:#4b7b1f22-3d91-4385-b2f4-ebdf1c0a6024">
<dcterms:modified rdf:resource="rdf:#c5c42e8c-4142-4672-a3a6-6760517ed8c2"/>
<rdf:value>
Updated metadata to conform to the 16/1/02 CellML Metadata 1.0
Specification.
</rdf:value>
<cmeta:modifier rdf:resource="rdf:#5be2f7ea-6223-4da2-a013-5daebcd9d2c8"/>
</rdf:Description>
<rdf:Description rdf:about="#MAPKK_P">
<dcterms:alternative>
phosphorylated mitogen-activated protein kinase kinase
</dcterms:alternative>
<dcterms:alternative>phosphorylated MAPK kinase</dcterms:alternative>
<dc:title>MAPKK_P</dc:title>
</rdf:Description>
<rdf:Description rdf:about="#MAPK">
<dcterms:alternative>
mitogen-activated protein kinase
</dcterms:alternative>
<dc:title>MAPK</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#ed29afb6-2ac6-45eb-9c6c-4d1f51456b52">
<vCard:Given>Chi-Ying</vCard:Given>
<vCard:Family>Huang</vCard:Family>
<vCard:Other>F</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#1342a8b2-fdea-4012-bc0e-1d3758c6ec23">
<dcterms:W3CDTF>2007-06-29T00:00:00+12:00</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="">
<dc:publisher>The University of Auckland, Bioengineering Research Group</dc:publisher>
<cmeta:comment rdf:resource="rdf:#74317f64-15c4-4ae2-96e0-d3c27a371d5e"/>
<dcterms:created rdf:resource="rdf:#1342a8b2-fdea-4012-bc0e-1d3758c6ec23"/>
<dc:creator rdf:resource="rdf:#34308850-7653-4d14-9548-31c3f4c7921b"/>
<cmeta:modification rdf:resource="rdf:#4ced4566-54a3-4c5b-aab4-5aaa34aef3a0"/>
<cmeta:modification rdf:resource="rdf:#24ff94d2-ea60-45ed-9c0c-d583c25a7185"/>
<cmeta:modification rdf:resource="rdf:#4b7b1f22-3d91-4385-b2f4-ebdf1c0a6024"/>
<cmeta:modification rdf:resource="rdf:#ee5b0d70-471f-41d1-b55f-67aee55fec3f"/>
<cmeta:modification rdf:resource="rdf:#f8e4f07e-c305-4f2a-a533-320df9bb3cb7"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#1a71e812-46dc-4577-becd-4a0b40a13023">
<vCard:Given>Catherine</vCard:Given>
<vCard:Family>Lloyd</vCard:Family>
<vCard:Other>May</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#a83a271f-0437-460a-a1d9-559066d90267">
<vCard:Orgname>The University of Auckland</vCard:Orgname>
<vCard:Orgunit>The Bioengineering Research Group</vCard:Orgunit>
</rdf:Description>
<rdf:Description rdf:about="rdf:#b7e67f47-a416-4ad6-8262-a16efde0d78b">
<dc:subject rdf:resource="rdf:#11c890df-2c3d-4870-abc5-eb48de4e0d6a"/>
</rdf:Description>
<rdf:Description rdf:about="#MAPKK_P_ase">
<dcterms:alternative>
mitogen-activated protein kinase kinase phosphatase
</dcterms:alternative>
<dcterms:alternative> MAPK kinase phosphatase</dcterms:alternative>
<dc:title>MAPKK_P_ase</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#1a5d8c3e-2fb2-4889-bc54-42edf4701f73">
<rdf:type rdf:resource="http://www.cellml.org/bqs/1.0#Person"/>
<vCard:N rdf:resource="rdf:#ed29afb6-2ac6-45eb-9c6c-4d1f51456b52"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#d8d17dd3-09e1-444f-ab40-d271cccb6858">
<rdf:type rdf:resource="http://www.cellml.org/bqs/1.0#Person"/>
<vCard:N rdf:resource="rdf:#e3d4f64a-5ffe-40da-a6f6-6e9d3ba1e374"/>
</rdf:Description>
<rdf:Description rdf:about="#E2">
<dcterms:alternative>
mitogen-activated protein kinase kinase kinase phosphatase
</dcterms:alternative>
<dcterms:alternative>MAPKKK_ deactivator</dcterms:alternative>
<dc:title>E2</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#74317f64-15c4-4ae2-96e0-d3c27a371d5e">
<dc:creator rdf:resource="rdf:#26d9bf1f-ed17-4528-9b92-e8c3e1d0460a"/>
<rdf:value>This model has been rebuilt using the differential rate equations that Ferrel et al. use in their paper to describe the signalling pathway. Rate parameters are dimensionless, corresponding with the zero order nature of the reactions in this pathway. This zero order ultrasensitivity arises when enzymes are operating at or near saturation. The conservation equations given in the paper are unable to be implemented, as they result in an overconstrained model. This model is known to run in PCEnv. </rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#E1">
<dcterms:alternative>
mitogen-activated protein kinase kinase kinase kinase
</dcterms:alternative>
<dcterms:alternative>MAPKKK activator</dcterms:alternative>
<dc:title>E1</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#c8c298d0-0495-4f1b-b63a-745eac03d1dc">
<dc:creator rdf:resource="rdf:#258e0e86-8090-423d-9d46-9e2100b326e6"/>
<dc:title>Ultrasensitivity in the mitogen-activated protein kinase cascade</dc:title>
<bqs:volume>93</bqs:volume>
<bqs:first_page>10078</bqs:first_page>
<bqs:Journal rdf:resource="rdf:#fb87db5f-55a8-4ca0-8617-e52795f11ec8"/>
<dcterms:issued rdf:resource="rdf:#fb205912-9a0a-4eea-a124-144f0030d8da"/>
<bqs:last_page>10083</bqs:last_page>
</rdf:Description>
<rdf:Description rdf:about="rdf:#649be6e2-0f84-469c-ac45-9f235136c26e">
<dcterms:W3CDTF>2007-06-29T12:23:21+12:00</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="#huang_ferrell_1996_version01">
<dc:title>
The mitogen-activated protein kinase (MAPK) cascade, 1996
</dc:title>
<cmeta:bio_entity>Oocyte</cmeta:bio_entity>
<cmeta:comment rdf:resource="rdf:#00ecd585-e3f7-425f-8896-da6bef3d1148"/>
<bqs:reference rdf:resource="rdf:#65f00587-ee1f-44d3-87b4-e7e1b8be07e5"/>
<bqs:reference rdf:resource="rdf:#b7e67f47-a416-4ad6-8262-a16efde0d78b"/>
<cmeta:species>Xenopus</cmeta:species>
</rdf:Description>
<rdf:Description rdf:about="rdf:#e81f7e5a-6a90-46b2-8bcd-9f1a3f641416">
<dcterms:W3CDTF>2003-04-09</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="rdf:#24ff94d2-ea60-45ed-9c0c-d583c25a7185">
<dcterms:modified rdf:resource="rdf:#9b385d0c-3d5f-4e08-8571-73486e37e88e"/>
<rdf:value>
Added more metadata.
</rdf:value>
<cmeta:modifier rdf:resource="rdf:#b4f1922b-4a2b-493c-af27-032f443d06bd"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#4ced4566-54a3-4c5b-aab4-5aaa34aef3a0">
<dcterms:modified rdf:resource="rdf:#649be6e2-0f84-469c-ac45-9f235136c26e"/>
<rdf:value>This model has been completely rebuilt using the differential rate equations described in Huang et al.'s paper. </rdf:value>
<cmeta:modifier rdf:resource="rdf:#e701e488-0c43-4e11-a40e-9ed70e525e92"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#9282263c-2e0f-440f-b006-9e5775e940c1">
<vCard:Given>James</vCard:Given>
<vCard:Family>Lawson</vCard:Family>
<vCard:Other>Richard</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#fb87db5f-55a8-4ca0-8617-e52795f11ec8">
<dc:title>Proceedings of the National Academy of Science, USA</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#329ae480-a36a-446b-9d47-e784a5e1a2f1">
<rdf:type rdf:resource="http://imc.org/vCard/3.0#internet"/>
<rdf:value>j.lawson@auckland.ac.nz</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="rdf:#8d7429c8-8597-4fc4-ab13-263e0c146f13">
<vCard:Given>Autumn</vCard:Given>
<vCard:Family>Cuellar</vCard:Family>
<vCard:Other>A</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="#MAPK_P">
<dcterms:alternative>
phosphorylated mitogen-activated protein kinase
</dcterms:alternative>
<dc:title>MAPK_P</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#26d9bf1f-ed17-4528-9b92-e8c3e1d0460a">
<vCard:FN>James Lawson</vCard:FN>
</rdf:Description>
<rdf:Description rdf:about="rdf:#e3d4f64a-5ffe-40da-a6f6-6e9d3ba1e374">
<vCard:Given>James</vCard:Given>
<vCard:Family>Ferrell</vCard:Family>
<vCard:Other>E</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#65f00587-ee1f-44d3-87b4-e7e1b8be07e5">
<bqs:Pubmed_id>8816754</bqs:Pubmed_id>
<bqs:JournalArticle rdf:resource="rdf:#c8c298d0-0495-4f1b-b63a-745eac03d1dc"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#ee5b0d70-471f-41d1-b55f-67aee55fec3f">
<dcterms:modified rdf:resource="rdf:#c4926013-b136-4f61-a838-e376f4323400"/>
<rdf:value>
Made changes to some of the metadata, bringing them up to date with
the most recent working draft (26th September) of the Metadata
Specification.
</rdf:value>
<cmeta:modifier rdf:resource="rdf:#6a7f76db-b28a-464e-9bee-3d44c752b950"/>
</rdf:Description>
<rdf:Description rdf:about="#MAPKK_PP">
<dcterms:alternative>
doubly phosphorylated MAPK kinase
</dcterms:alternative>
<dcterms:alternative>
doubly phosphorylated mitogen-activated protein kinase kinase
</dcterms:alternative>
<dc:title>MAPKK_PP</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#11c890df-2c3d-4870-abc5-eb48de4e0d6a">
<bqs:subject_type>keyword</bqs:subject_type>
<rdf:value rdf:resource="rdf:#eba8c7ef-3b79-452e-b009-7d341b82f7ee"/>
</rdf:Description>
</rdf:RDF>
</model>
