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This CellML file was generated on 20/06/2007 at 12:39:18 at a.m. using:
COR (0.9.31.649)
Copyright 2002-2007 Dr Alan Garny
http://COR.physiol.ox.ac.uk/ - COR@physiol.ox.ac.uk
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http://www.CellML.org/
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<title>Emergent properties of networks of biological signaling pathways</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Auckland Bioengineering Institute, The University of Auckland</shortaffil>
</affiliation>
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<section id="sec_status">
<title>Model Status</title>
<para>
This version of the model describes the complete network of signalling pathways in the original publication. This model is able to be solved but does not give the correct results as it is not connected to the other modules of the pathway. ValidateCellML verifies this model as valid CellML but detects unit inconsistencies.
</para>
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<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
ABSTRACT: Many distinct signaling pathways allow the cell to receive, process, and respond to information. Often, components of different pathways interact, resulting in signaling networks. Biochemical signaling networks were constructed with experimentally obtained constants and analyzed by computational methods to understand their role in complex biological processes. These networks exhibit emergent properties such as integration of signals across multiple time scales, generation of distinct outputs depending on input strength and duration, and self-sustaining feedback loops. Feedback can result in bistable behavior with discrete steady-state activities, well-defined input thresholds for transition between states and prolonged signal output, and signal modulation in response to transient stimuli. These properties of signaling networks raise the possibility that information for "learned behavior" of biological systems may be stored within intracellular biochemical reactions that comprise signaling pathways.
</para>
<para>
The original paper reference is cited below:
</para>
<para>
Emergent properties of networks of biological signaling pathways. Bhalla US, Iyengar R.
<emphasis>Science</emphasis> 1999 Jan 15; 283(5400); 381-7. <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9888852&dopt=Abstract">PubMed ID: 9888852</ulink>
</para>
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<caption>A rendering of the complete signalling network.</caption>
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<ci>GEF</ci>
</apply>
<apply>
<plus/>
<ci>kmB1</ci>
<ci>GEF</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>PKC</ci>
<ci>VmaxB6</ci>
<ci>GEF</ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>kmB6</ci>
<apply>
<plus/>
<ci>one</ci>
<apply>
<divide/>
<ci>GAP</ci>
<ci>kmB3</ci>
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<divide/>
<ci>Ng</ci>
<ci>kmM7</ci>
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<apply>
<divide/>
<ci>Raf</ci>
<ci>kmH1</ci>
</apply>
<apply>
<divide/>
<ci>NgCaM</ci>
<ci>kmM8</ci>
</apply>
</apply>
</apply>
<ci>GEF</ci>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci>kfB2</ci>
<ci>GEF_inact</ci>
</apply>
</apply>
<apply>
<times/>
<ci>kfB7</ci>
<ci>GEF_star</ci>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci>kfB5</ci>
<ci>Ca4CAM</ci>
<ci>GEF</ci>
</apply>
</apply>
<apply>
<times/>
<ci>kbB5</ci>
<ci>CaM_GEF</ci>
</apply>
</apply>
<apply>
<times/>
<ci>kfB8</ci>
<ci>GEF</ci>
<ci>Gbg</ci>
</apply>
</apply>
<apply>
<times/>
<ci>kbB8</ci>
<ci>Gbg_GEF</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>CaM_GEF</ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<apply>
<minus/>
<ci>kbB5</ci>
</apply>
<ci>CaM_GEF</ci>
</apply>
<apply>
<times/>
<ci>kfB5</ci>
<ci>GEF</ci>
<ci>Ca4CAM</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>Ca4CAM</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<apply>
<minus/>
<ci>kbB5</ci>
</apply>
<ci>CaM_GEF</ci>
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<apply>
<times/>
<ci>kfB5</ci>
<ci>GEF</ci>
<ci>Ca4CAM</ci>
</apply>
</apply>
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<apply>
<times/>
<ci>Ca</ci>
<ci>Ca3CaM</ci>
<ci>kfM3</ci>
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<apply>
<times/>
<ci>kbM3</ci>
<ci>Ca4CAM</ci>
</apply>
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<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>Gbg_GEF</ci>
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<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<apply>
<minus/>
<ci>kfB8</ci>
</apply>
<ci>GEF</ci>
<ci>Gbg</ci>
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<apply>
<times/>
<ci>kbB8</ci>
<ci>Gbg_GEF</ci>
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<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>GEF_star</ci>
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<apply>
<minus/>
<apply>
<divide/>
<apply>
<times/>
<ci>PKC</ci>
<ci>VmaxB6</ci>
<ci>GEF</ci>
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<apply>
<plus/>
<apply>
<times/>
<ci>kmB6</ci>
<apply>
<plus/>
<ci>one</ci>
<apply>
<divide/>
<ci>GAP</ci>
<ci>kmB3</ci>
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<divide/>
<ci>Ng</ci>
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<divide/>
<ci>Raf</ci>
<ci>kmH1</ci>
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<apply>
<divide/>
<ci>NgCaM</ci>
<ci>kmM8</ci>
</apply>
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<ci>GEF</ci>
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<apply>
<times/>
<ci>kfB7</ci>
<ci>GEF_star</ci>
</apply>
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</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>CaM</ci>
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<apply>
<plus/>
<apply>
<minus/>
<apply>
<minus/>
<apply>
<minus/>
<apply>
<times/>
<ci>kfM1</ci>
<ci>Ca</ci>
<ci>Ca</ci>
<ci>CaM</ci>
</apply>
<apply>
<times/>
<ci>kbM1</ci>
<ci>Ca2CaM</ci>
</apply>
</apply>
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<apply>
<minus/>
<apply>
<times/>
<ci>kfM4</ci>
<ci>Ng</ci>
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</apply>
<apply>
<times/>
<ci>kbM4</ci>
<ci>NgCaM</ci>
</apply>
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<apply>
<divide/>
<apply>
<times/>
<ci>NgCaM</ci>
<ci>PKC</ci>
<ci>VmaxM8</ci>
</apply>
<apply>
<plus/>
<ci>NgCaM</ci>
<ci>kmM8</ci>
</apply>
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<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>NgCaM</ci>
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<apply>
<minus/>
<apply>
<minus/>
<apply>
<times/>
<ci>kfM4</ci>
<ci>Ng</ci>
<ci>CaM</ci>
</apply>
<apply>
<times/>
<ci>kbM4</ci>
<ci>NgCaM</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>NgCaM</ci>
<ci>PKC</ci>
<ci>VmaxM8</ci>
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<apply>
<plus/>
<ci>NgCaM</ci>
<apply>
<times/>
<ci>kmM8</ci>
<apply>
<plus/>
<ci>one</ci>
<apply>
<divide/>
<ci>GAP</ci>
<ci>kmB3</ci>
</apply>
<apply>
<divide/>
<ci>GEF</ci>
<ci>kmB6</ci>
</apply>
<apply>
<divide/>
<ci>Raf</ci>
<ci>kmH1</ci>
</apply>
<apply>
<divide/>
<ci>Ng</ci>
<ci>kmM7</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
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<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>Ca2CaM</ci>
</apply>
<apply>
<minus/>
<apply>
<minus/>
<apply>
<times/>
<ci>kfM1</ci>
<ci>Ca</ci>
<ci>Ca</ci>
<ci>CaM</ci>
</apply>
<apply>
<times/>
<ci>kbM1</ci>
<ci>Ca2CaM</ci>
</apply>
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<apply>
<minus/>
<apply>
<times/>
<ci>Ca</ci>
<ci>Ca2CaM</ci>
<ci>kfM2</ci>
</apply>
<apply>
<times/>
<ci>kbM2</ci>
<ci>Ca3CaM</ci>
</apply>
</apply>
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<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
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<ci>Ca3CaM</ci>
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<apply>
<minus/>
<apply>
<minus/>
<apply>
<times/>
<ci>Ca</ci>
<ci>Ca2CaM</ci>
<ci>kfM2</ci>
</apply>
<apply>
<times/>
<ci>kbM2</ci>
<ci>Ca3CaM</ci>
</apply>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>Ca</ci>
<ci>Ca3CaM</ci>
<ci>kfM3</ci>
</apply>
<apply>
<times/>
<ci>kbM3</ci>
<ci>Ca4CAM</ci>
</apply>
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<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
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<ci>Ng_star</ci>
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<apply>
<plus/>
<apply>
<minus/>
<apply>
<minus/>
<apply>
<divide/>
<apply>
<times/>
<ci>NgCaM</ci>
<ci>PKC</ci>
<ci>VmaxM8</ci>
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<plus/>
<ci>NgCaM</ci>
<apply>
<times/>
<ci>kmM8</ci>
<apply>
<plus/>
<ci>one</ci>
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<divide/>
<ci>GAP</ci>
<ci>kmB3</ci>
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<apply>
<divide/>
<ci>GEF</ci>
<ci>kmB6</ci>
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<divide/>
<ci>Raf</ci>
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<apply>
<divide/>
<ci>Ng</ci>
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</apply>
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<apply>
<times/>
<ci>kfM6</ci>
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<apply>
<divide/>
<apply>
<times/>
<ci>VmaxM5</ci>
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<apply>
<plus/>
<ci>Ng_star</ci>
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<times/>
<ci>Ng</ci>
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<ci>Ng</ci>
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<times/>
<ci>kmM7</ci>
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<plus/>
<ci>one</ci>
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<ci>kmB3</ci>
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<ci>GEF</ci>
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<ci>Ng</ci>
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<times/>
<ci>kfM6</ci>
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<times/>
<ci>VmaxM5</ci>
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<ci>Ng_star</ci>
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<ci>Ng</ci>
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<times/>
<ci>kmM7</ci>
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<plus/>
<ci>one</ci>
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<divide/>
<ci>GAP</ci>
<ci>kmB3</ci>
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<divide/>
<ci>GEF</ci>
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<divide/>
<ci>NgCaM</ci>
<ci>kmM8</ci>
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</apply>
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</apply>
</apply>
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<variable units="um" public_interface="in" name="SHCstar_SOS_GRB2"/>
<variable units="um" public_interface="in" name="MAPK_star"/>
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<variable units="per_s" name="VmaxH4" initial_value="6"/>
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<variable units="um" name="kmH9" initial_value="15.6565"/>
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<bvar>
<ci>t</ci>
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<minus/>
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<plus/>
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<minus/>
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<apply>
<minus/>
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<ci>Gbg_GEF</ci>
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<ci>SHCstar_SOS_GRB2</ci>
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<ci>kfH5</ci>
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<ci>GTPRasRaf_star</ci>
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<minus/>
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<minus/>
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<apply>
<minus/>
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<ci>Gbg_GEF</ci>
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<ci>GDP_RAS</ci>
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<diff/>
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<divide/>
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<apply>
<minus/>
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<plus/>
<apply>
<times/>
<ci>kmB3</ci>
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<plus/>
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<ci>kmH1</ci>
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<ci>kmM8</ci>
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<apply>
<times/>
<ci>kfB4</ci>
<ci>GAPstar</ci>
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<apply>
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<apply>
<diff/>
<bvar>
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<apply>
<minus/>
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<divide/>
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<ci>PKC</ci>
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<apply>
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<plus/>
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<ci>kmM7</ci>
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<apply>
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</apply>
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<ci>GAP</ci>
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</apply>
<apply>
<times/>
<ci>kfB4</ci>
<ci>GAPstar</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>GTPRasRaf_star</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>GTP_RAS</ci>
<ci>Raf_star</ci>
<ci>kfH5</ci>
</apply>
<apply>
<times/>
<ci>GTPRasRaf_star</ci>
<ci>kbH5</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>Raf</ci>
</apply>
<apply>
<plus/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<ci>PKC</ci>
</apply>
<ci>Raf</ci>
<ci>VmaxH1</ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>kmH1</ci>
<apply>
<plus/>
<ci>one</ci>
<apply>
<divide/>
<ci>GAP</ci>
<ci>kmB3</ci>
</apply>
<apply>
<divide/>
<ci>GEF</ci>
<ci>kmB6</ci>
</apply>
<apply>
<divide/>
<ci>Ng</ci>
<ci>kmM7</ci>
</apply>
<apply>
<divide/>
<ci>NgCaM</ci>
<ci>kmM8</ci>
</apply>
</apply>
</apply>
<ci>Raf</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>Raf_star</ci>
<ci>PP2A</ci>
<ci>VmaxH3</ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>kmH3</ci>
<apply>
<plus/>
<ci>one</ci>
<apply>
<divide/>
<ci>Raf_star_star</ci>
<ci>kmH4</ci>
</apply>
<apply>
<divide/>
<ci>MAPKK_star_star</ci>
<ci>kmH9</ci>
</apply>
<apply>
<divide/>
<ci>MAPKK_star</ci>
<ci>kmH8</ci>
</apply>
</apply>
</apply>
<ci>Raf_star</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>Raf_star</ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<minus/>
<apply>
<divide/>
<apply>
<times/>
<ci>PKC</ci>
<ci>Raf</ci>
<ci>VmaxH1</ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>kmH1</ci>
<apply>
<plus/>
<ci>one</ci>
<apply>
<divide/>
<ci>GAP</ci>
<ci>kmB3</ci>
</apply>
<apply>
<divide/>
<ci>GEF</ci>
<ci>kmB6</ci>
</apply>
<apply>
<divide/>
<ci>Ng</ci>
<ci>kmM7</ci>
</apply>
<apply>
<divide/>
<ci>NgCaM</ci>
<ci>kmM8</ci>
</apply>
</apply>
</apply>
<ci>Raf</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>Raf_star</ci>
<ci>PP2A</ci>
<ci>VmaxH3</ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>kmH3</ci>
<apply>
<plus/>
<ci>one</ci>
<apply>
<divide/>
<ci>Raf_star_star</ci>
<ci>kmH4</ci>
</apply>
<apply>
<divide/>
<ci>MAPKK_star_star</ci>
<ci>kmH9</ci>
</apply>
<apply>
<divide/>
<ci>MAPKK_star</ci>
<ci>kmH8</ci>
</apply>
</apply>
</apply>
<ci>Raf_star</ci>
</apply>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>Raf_star</ci>
<ci>MAPK_star</ci>
<ci>VmaxH2</ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>kmH2</ci>
<apply>
<plus/>
<ci>one</ci>
<apply>
<divide/>
<ci>SOS</ci>
<ci>kmA9</ci>
</apply>
</apply>
</apply>
<ci>Raf_star</ci>
</apply>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>Raf_star_star</ci>
<ci>PP2A</ci>
<ci>VmaxH4</ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>kmH4</ci>
<apply>
<plus/>
<ci>one</ci>
<apply>
<divide/>
<ci>Raf_star</ci>
<ci>kmH3</ci>
</apply>
<apply>
<divide/>
<ci>MAPKK_star_star</ci>
<ci>kmH9</ci>
</apply>
<apply>
<divide/>
<ci>MAPKK_star</ci>
<ci>kmH8</ci>
</apply>
</apply>
</apply>
<ci>Raf_star_star</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>Raf_star_star</ci>
</apply>
<apply>
<minus/>
<apply>
<divide/>
<apply>
<times/>
<ci>Raf_star</ci>
<ci>MAPK_star</ci>
<ci>VmaxH2</ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>kmH2</ci>
<apply>
<plus/>
<ci>one</ci>
<apply>
<divide/>
<ci>SOS</ci>
<ci>kmA9</ci>
</apply>
</apply>
</apply>
<ci>Raf_star</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>Raf_star_star</ci>
<ci>PP2A</ci>
<ci>VmaxH4</ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>kmH4</ci>
<apply>
<plus/>
<ci>one</ci>
<apply>
<divide/>
<ci>Raf_star</ci>
<ci>kmH3</ci>
</apply>
<apply>
<divide/>
<ci>MAPKK_star_star</ci>
<ci>kmH9</ci>
</apply>
<apply>
<divide/>
<ci>MAPKK_star</ci>
<ci>kmH8</ci>
</apply>
</apply>
</apply>
<ci>Raf_star_star</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="H_Model_Module_MAPKK">
<variable units="s" public_interface="in" name="t"/>
<variable units="um" public_interface="in" name="GTPRasRaf_star"/>
<variable units="um" public_interface="in" name="Raf_star"/>
<variable units="um" public_interface="in" name="Raf_star_star"/>
<variable units="um" public_interface="out" name="MAPKK_star" initial_value="0"/>
<variable units="um" public_interface="out" name="MAPKK_star_star" initial_value="0"/>
<variable units="um" name="MAPKK" initial_value="0.18"/>
<variable units="um" name="PP2A" initial_value="0.224"/>
<variable units="dimensionless" name="one" initial_value="1"/>
<variable units="um" name="kmH6" initial_value="0.159091667"/>
<variable units="um" name="kmH7" initial_value="0.159091667"/>
<variable units="um" name="kmH8" initial_value="15.6565"/>
<variable units="um" name="kmH9" initial_value="15.6565"/>
<variable units="per_s" name="VmaxH6" initial_value="0.105"/>
<variable units="per_s" name="VmaxH7" initial_value="0.105"/>
<variable units="per_s" name="VmaxH8" initial_value="6"/>
<variable units="per_s" name="VmaxH9" initial_value="6"/>
<variable units="um" name="kmH3" initial_value="15.6565"/>
<variable units="um" name="kmH4" initial_value="15.6565"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>MAPKK</ci>
</apply>
<apply>
<plus/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<ci>MAPKK</ci>
</apply>
<ci>VmaxH6</ci>
<ci>GTPRasRaf_star</ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>kmH6</ci>
<apply>
<plus/>
<ci>one</ci>
<apply>
<divide/>
<ci>MAPKK_star</ci>
<ci>kmH7</ci>
</apply>
</apply>
</apply>
<ci>MAPKK</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>MAPKK_star</ci>
<ci>VmaxH8</ci>
<ci>PP2A</ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>kmH8</ci>
<apply>
<plus/>
<ci>one</ci>
<apply>
<divide/>
<ci>Raf_star</ci>
<ci>kmH3</ci>
</apply>
<apply>
<divide/>
<ci>Raf_star_star</ci>
<ci>kmH4</ci>
</apply>
<apply>
<divide/>
<ci>MAPKK_star_star</ci>
<ci>kmH9</ci>
</apply>
</apply>
</apply>
<ci>MAPKK_star</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>MAPKK_star</ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<minus/>
<apply>
<divide/>
<apply>
<times/>
<ci>MAPKK</ci>
<ci>VmaxH6</ci>
<ci>GTPRasRaf_star</ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>kmH6</ci>
<apply>
<plus/>
<ci>one</ci>
<apply>
<divide/>
<ci>MAPKK_star</ci>
<ci>kmH7</ci>
</apply>
</apply>
</apply>
<ci>MAPKK</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>MAPKK_star</ci>
<ci>VmaxH8</ci>
<ci>PP2A</ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>kmH8</ci>
<apply>
<plus/>
<ci>one</ci>
<apply>
<divide/>
<ci>Raf_star</ci>
<ci>kmH3</ci>
</apply>
<apply>
<divide/>
<ci>Raf_star_star</ci>
<ci>kmH4</ci>
</apply>
<apply>
<divide/>
<ci>MAPKK_star_star</ci>
<ci>kmH9</ci>
</apply>
</apply>
</apply>
<ci>MAPKK_star</ci>
</apply>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>MAPKK_star</ci>
<ci>VmaxH7</ci>
<ci>GTPRasRaf_star</ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>kmH7</ci>
<apply>
<plus/>
<ci>one</ci>
<apply>
<divide/>
<ci>MAPKK</ci>
<ci>kmH6</ci>
</apply>
</apply>
</apply>
<ci>MAPKK_star</ci>
</apply>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>MAPKK_star_star</ci>
<ci>VmaxH9</ci>
<ci>PP2A</ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>kmH9</ci>
<apply>
<plus/>
<ci>one</ci>
<apply>
<divide/>
<ci>Raf_star</ci>
<ci>kmH3</ci>
</apply>
<apply>
<divide/>
<ci>Raf_star_star</ci>
<ci>kmH4</ci>
</apply>
<apply>
<divide/>
<ci>MAPKK_star</ci>
<ci>kmH8</ci>
</apply>
</apply>
</apply>
<ci>MAPKK_star_star</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>MAPKK_star_star</ci>
</apply>
<apply>
<minus/>
<apply>
<divide/>
<apply>
<times/>
<ci>MAPKK_star</ci>
<ci>VmaxH7</ci>
<ci>GTPRasRaf_star</ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>kmH7</ci>
<apply>
<plus/>
<ci>one</ci>
<apply>
<divide/>
<ci>MAPKK</ci>
<ci>kmH6</ci>
</apply>
</apply>
</apply>
<ci>MAPKK_star</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>MAPKK_star_star</ci>
<ci>VmaxH9</ci>
<ci>PP2A</ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>kmH9</ci>
<apply>
<plus/>
<ci>one</ci>
<apply>
<divide/>
<ci>Raf_star</ci>
<ci>kmH3</ci>
</apply>
<apply>
<divide/>
<ci>Raf_star_star</ci>
<ci>kmH4</ci>
</apply>
<apply>
<divide/>
<ci>MAPKK_star</ci>
<ci>kmH8</ci>
</apply>
</apply>
</apply>
<ci>MAPKK_star_star</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="H_Model_Module_MAPK">
<variable units="s" public_interface="in" name="t"/>
<variable units="um" public_interface="in" name="MAPKK_star_star"/>
<variable units="um" public_interface="out" name="MAPK_star" initial_value="0"/>
<variable units="um" public_interface="out" name="MAPK" initial_value="0.36"/>
<variable units="um" name="MAPK_tyr" initial_value="0"/>
<variable units="um" name="MKP1" initial_value="0.032"/>
<variable units="dimensionless" name="one" initial_value="1"/>
<variable units="um" name="kmH10" initial_value="0.046296667"/>
<variable units="um" name="kmH11" initial_value="0.046296667"/>
<variable units="um" name="kmH12" initial_value="0.066666667"/>
<variable units="um" name="kmH13" initial_value="0.066666667"/>
<variable units="per_s" name="VmaxH10" initial_value="0.15"/>
<variable units="per_s" name="VmaxH11" initial_value="0.15"/>
<variable units="per_s" name="VmaxH12" initial_value="1"/>
<variable units="per_s" name="VmaxH13" initial_value="1"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>MAPK</ci>
</apply>
<apply>
<plus/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<ci>MAPK</ci>
</apply>
<ci>VmaxH10</ci>
<ci>MAPKK_star_star</ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>kmH10</ci>
<apply>
<plus/>
<ci>one</ci>
<apply>
<divide/>
<ci>MAPK_tyr</ci>
<ci>kmH11</ci>
</apply>
</apply>
</apply>
<ci>MAPK</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>MAPK_tyr</ci>
<ci>VmaxH12</ci>
<ci>MKP1</ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>kmH12</ci>
<apply>
<plus/>
<ci>one</ci>
<apply>
<divide/>
<ci>MAPK_star</ci>
<ci>kmH13</ci>
</apply>
</apply>
</apply>
<ci>MAPK_tyr</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>MAPK_tyr</ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<minus/>
<apply>
<divide/>
<apply>
<times/>
<ci>MAPK</ci>
<ci>VmaxH10</ci>
<ci>MAPKK_star_star</ci>
</apply>
<apply>
<plus/>
<apply>
<divide/>
<apply>
<times/>
<ci>kmH10</ci>
<ci>MAPK_tyr</ci>
</apply>
<ci>kmH11</ci>
</apply>
<ci>MAPK</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>MAPK_tyr</ci>
<ci>VmaxH12</ci>
<ci>MKP1</ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>kmH12</ci>
<apply>
<plus/>
<ci>one</ci>
<apply>
<divide/>
<ci>MAPK_star</ci>
<ci>kmH13</ci>
</apply>
</apply>
</apply>
<ci>MAPK_tyr</ci>
</apply>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>MAPK_tyr</ci>
<ci>VmaxH11</ci>
<ci>MAPKK_star_star</ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>kmH11</ci>
<apply>
<plus/>
<ci>one</ci>
<apply>
<divide/>
<ci>MAPK_tyr</ci>
<ci>kmH12</ci>
</apply>
</apply>
</apply>
<ci>MAPK_tyr</ci>
</apply>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>MAPK_star</ci>
<ci>VmaxH13</ci>
<ci>MKP1</ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>kmH13</ci>
<apply>
<plus/>
<ci>one</ci>
<apply>
<divide/>
<ci>MAPK_tyr</ci>
<ci>kmH12</ci>
</apply>
</apply>
</apply>
<ci>MAPK_star</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>MAPK_star</ci>
</apply>
<apply>
<minus/>
<apply>
<divide/>
<apply>
<times/>
<ci>MAPK_tyr</ci>
<ci>VmaxH11</ci>
<ci>MAPKK_star_star</ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>kmH11</ci>
<apply>
<plus/>
<ci>one</ci>
<apply>
<divide/>
<ci>MAPK</ci>
<ci>kmH10</ci>
</apply>
</apply>
</apply>
<ci>MAPK_tyr</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>MAPK_star</ci>
<ci>VmaxH13</ci>
<ci>MKP1</ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>kmH13</ci>
<apply>
<plus/>
<ci>one</ci>
<apply>
<divide/>
<ci>MAPK_tyr</ci>
<ci>kmH12</ci>
</apply>
</apply>
</apply>
<ci>MAPK_star</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="A_Model_Module_SHC">
<variable units="s" public_interface="in" name="t"/>
<variable units="um" public_interface="in" name="EGF_EGFR"/>
<variable units="um" public_interface="in" name="MAPK_star"/>
<variable units="um" public_interface="in" name="Raf_star"/>
<variable units="um" public_interface="in" name="CaPLCg"/>
<variable units="um" public_interface="out" name="SOS" initial_value="0.1"/>
<variable units="um" public_interface="out" name="SHCstar_SOS_GRB2" initial_value="0"/>
<variable units="um" public_interface="out" name="SHC" initial_value="0.5"/>
<variable units="um" name="SHCstar" initial_value="0"/>
<variable units="um" name="SOSstar_GRB2" initial_value="0"/>
<variable units="um" name="SOS_GRB2" initial_value="0"/>
<variable units="um" name="GRB2" initial_value="1"/>
<variable units="um" name="SOSstar" initial_value="0"/>
<variable units="dimensionless" name="one" initial_value="1"/>
<variable units="um" name="kmA3" initial_value="0.83333333333"/>
<variable units="per_s" name="kfA4" initial_value="0.0016667"/>
<variable units="per_s" name="kbA4" initial_value="0"/>
<variable units="per_um_s" name="kfA5" initial_value="0.000000041667"/>
<variable units="per_s" name="kbA5" initial_value="0.0168"/>
<variable units="per_um_s" name="kfA6" initial_value="0.0000008333"/>
<variable units="per_s" name="kbA6" initial_value="0.1"/>
<variable units="per_s" name="kfA8" initial_value="0.001"/>
<variable units="per_s" name="kbA8" initial_value="0"/>
<variable units="per_um_s" name="kfA10" initial_value="0.000000041667"/>
<variable units="per_s" name="kbA10" initial_value="0.0168"/>
<variable units="um" name="kmA7" initial_value="0.40404"/>
<variable units="um" name="kmA9" initial_value="2.564166667"/>
<variable units="per_s" name="VmaxA7" initial_value="0.02"/>
<variable units="per_s" name="VmaxA3" initial_value="0.2"/>
<variable units="per_s" name="VmaxA9" initial_value="10"/>
<variable units="um" name="kmH2" initial_value="25.64166667"/>
<variable units="um" name="kmF4" initial_value="0.33333333333"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>SHCstar</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<divide/>
<apply>
<times/>
<ci>EGF_EGFR</ci>
<ci>VmaxA3</ci>
<ci>SHC</ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>kmA3</ci>
<apply>
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<apply>
<minus/>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<minus/>
<apply>
<times/>
<ci>PKC_i</ci>
<ci>Ca</ci>
<ci>kfK7</ci>
</apply>
<apply>
<times/>
<ci>CaPKC</ci>
<ci>kbK7</ci>
</apply>
</apply>
<apply>
<times/>
<ci>CaPKC</ci>
<ci>kfK3</ci>
</apply>
</apply>
<apply>
<times/>
<ci>PKC</ci>
<ci>kbK3</ci>
</apply>
</apply>
<apply>
<times/>
<ci>CaPKC</ci>
<ci>AA</ci>
<ci>kfK4</ci>
</apply>
</apply>
<apply>
<times/>
<ci>PKC</ci>
<ci>kbK4</ci>
</apply>
</apply>
<apply>
<times/>
<ci>DAG</ci>
<ci>CaPKC</ci>
<ci>kfK8</ci>
</apply>
</apply>
<apply>
<times/>
<ci>DAGCaPKC</ci>
<ci>kbK8</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>DAGCaPKC</ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<minus/>
<apply>
<times/>
<ci>DAG</ci>
<ci>CaPKC</ci>
<ci>kfK8</ci>
</apply>
<apply>
<times/>
<ci>DAGCaPKC</ci>
<ci>kbK8</ci>
</apply>
</apply>
<apply>
<times/>
<ci>DAGCaPKC</ci>
<ci>kfK5</ci>
</apply>
</apply>
<apply>
<times/>
<ci>PKC</ci>
<ci>kbK5</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>PKC</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<times/>
<ci>PKC_i</ci>
<ci>kfK1</ci>
</apply>
<apply>
<times/>
<ci>PKC</ci>
<ci>kbK1</ci>
</apply>
</apply>
<apply>
<times/>
<ci>PKC_i</ci>
<ci>AA</ci>
<ci>kfK2</ci>
</apply>
</apply>
<apply>
<times/>
<ci>PKC</ci>
<ci>kbK2</ci>
</apply>
</apply>
<apply>
<times/>
<ci>CaPKC</ci>
<ci>kfK3</ci>
</apply>
</apply>
<apply>
<times/>
<ci>PKC</ci>
<ci>kbK3</ci>
</apply>
</apply>
<apply>
<times/>
<ci>CaPKC</ci>
<ci>AA</ci>
<ci>kfK4</ci>
</apply>
</apply>
<apply>
<times/>
<ci>PKC</ci>
<ci>kbK4</ci>
</apply>
</apply>
<apply>
<times/>
<ci>DAGCaPKC</ci>
<ci>kfK5</ci>
</apply>
</apply>
<apply>
<times/>
<ci>PKC</ci>
<ci>kbK5</ci>
</apply>
</apply>
<apply>
<times/>
<ci>AADAGPKC</ci>
<ci>kfK6</ci>
</apply>
</apply>
<apply>
<times/>
<ci>PKC</ci>
<ci>kbK6</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>AA</ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<apply>
<minus/>
<ci>PKC_i</ci>
</apply>
<ci>AA</ci>
<ci>kfK2</ci>
</apply>
<apply>
<times/>
<ci>PKC</ci>
<ci>kbK2</ci>
</apply>
</apply>
<apply>
<times/>
<ci>CaPKC</ci>
<ci>AA</ci>
<ci>kfK4</ci>
</apply>
</apply>
<apply>
<times/>
<ci>PKC</ci>
<ci>kbK4</ci>
</apply>
</apply>
<apply>
<times/>
<ci>DAGPKC</ci>
<ci>AA</ci>
<ci>kfK10</ci>
</apply>
</apply>
<apply>
<times/>
<ci>AADAGPKC</ci>
<ci>kbK10</ci>
</apply>
</apply>
<apply>
<times/>
<ci>AA</ci>
<ci>kfE13</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>CaPLA2_star</ci>
<ci>VmaxE12</ci>
<ci>APC</ci>
</apply>
<apply>
<plus/>
<ci>kmE12</ci>
<ci>APC</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>CaPLA2</ci>
<ci>VmaxE4</ci>
<ci>APC</ci>
</apply>
<apply>
<plus/>
<ci>kmE4</ci>
<ci>APC</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>DAGCaPLA2</ci>
<ci>VmaxE8</ci>
<ci>APC</ci>
</apply>
<apply>
<plus/>
<ci>kmE8</ci>
<ci>APC</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>PIP2CaPLA2</ci>
<ci>VmaxE6</ci>
<ci>APC</ci>
</apply>
<apply>
<plus/>
<ci>kmE6</ci>
<ci>APC</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>PIP2PLA2</ci>
<ci>VmaxE2</ci>
<ci>APC</ci>
</apply>
<apply>
<plus/>
<ci>kmE2</ci>
<ci>APC</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>PLA2_cyt</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<times/>
<ci>PLA2_star</ci>
<ci>kfE10</ci>
</apply>
<apply>
<times/>
<ci>PIP2_star</ci>
<ci>PLA2_cyt</ci>
<ci>kfE1</ci>
</apply>
</apply>
<apply>
<times/>
<ci>PIP2PLA2</ci>
<ci>kbE1</ci>
</apply>
</apply>
<apply>
<times/>
<ci>Ca</ci>
<ci>PLA2_cyt</ci>
<ci>kfE3</ci>
</apply>
</apply>
<apply>
<times/>
<ci>CaPLA2</ci>
<ci>kbE3</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>MAPK</ci>
<ci>VmaxE9</ci>
<ci>PLA2_cyt</ci>
</apply>
<apply>
<plus/>
<ci>kmE9</ci>
<ci>PLA2_cyt</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>PIP2PLA2</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>PIP2_star</ci>
<ci>PLA2_cyt</ci>
<ci>kfE1</ci>
</apply>
<apply>
<times/>
<ci>PIP2PLA2</ci>
<ci>kbE1</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>PIP2_star</ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<apply>
<minus/>
<ci>PIP2_star</ci>
</apply>
<ci>PLA2_cyt</ci>
<ci>kfE1</ci>
</apply>
<apply>
<times/>
<ci>PIP2PLA2</ci>
<ci>kbE1</ci>
</apply>
</apply>
<apply>
<times/>
<ci>PIP2_star</ci>
<ci>CaPLA2</ci>
<ci>kfE5</ci>
</apply>
</apply>
<apply>
<times/>
<ci>PIP2CaPLA2</ci>
<ci>kbE5</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>PLA2_star</ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<apply>
<minus/>
<ci>PLA2_star</ci>
</apply>
<ci>kfE10</ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>MAPK</ci>
<ci>VmaxE9</ci>
<ci>PLA2_cyt</ci>
</apply>
<apply>
<plus/>
<ci>kmE9</ci>
<ci>PLA2_cyt</ci>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci>Ca</ci>
<ci>PLA2_star</ci>
<ci>kfE11</ci>
</apply>
</apply>
<apply>
<times/>
<ci>CaPLA2_star</ci>
<ci>kbE11</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>CaPLA2_star</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>Ca</ci>
<ci>PLA2_star</ci>
<ci>kfE11</ci>
</apply>
<apply>
<times/>
<ci>CaPLA2_star</ci>
<ci>kbE11</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>CaPLA2</ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<minus/>
<apply>
<times/>
<ci>Ca</ci>
<ci>PLA2_cyt</ci>
<ci>kfE3</ci>
</apply>
<apply>
<times/>
<ci>CaPLA2</ci>
<ci>kbE3</ci>
</apply>
</apply>
<apply>
<times/>
<ci>DAG</ci>
<ci>CaPLA2</ci>
<ci>kfE7</ci>
</apply>
</apply>
<apply>
<times/>
<ci>DAGCaPLA2</ci>
<ci>kbE7</ci>
</apply>
</apply>
<apply>
<times/>
<ci>PIP2_star</ci>
<ci>CaPLA2</ci>
<ci>kfE5</ci>
</apply>
</apply>
<apply>
<times/>
<ci>PIP2CaPLA2</ci>
<ci>kbE5</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>PIP2CaPLA2</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>PIP2_star</ci>
<ci>CaPLA2</ci>
<ci>kfE5</ci>
</apply>
<apply>
<times/>
<ci>PIP2CaPLA2</ci>
<ci>kbE5</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>DAGCaPLA2</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>DAG</ci>
<ci>CaPLA2</ci>
<ci>kfE7</ci>
</apply>
<apply>
<times/>
<ci>DAGCaPLA2</ci>
<ci>kbE7</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>APC</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>AA</ci>
<ci>kfE13</ci>
</apply>
<apply>
<plus/>
<apply>
<divide/>
<apply>
<times/>
<ci>CaPLA2_star</ci>
<ci>VmaxE12</ci>
<ci>APC</ci>
</apply>
<apply>
<plus/>
<ci>kmE12</ci>
<ci>APC</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>CaPLA2</ci>
<ci>VmaxE4</ci>
<ci>APC</ci>
</apply>
<apply>
<plus/>
<ci>kmE4</ci>
<ci>APC</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>DAGCaPLA2</ci>
<ci>VmaxE8</ci>
<ci>APC</ci>
</apply>
<apply>
<plus/>
<ci>kmE8</ci>
<ci>APC</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>PIP2CaPLA2</ci>
<ci>VmaxE6</ci>
<ci>APC</ci>
</apply>
<apply>
<plus/>
<ci>kmE6</ci>
<ci>APC</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>PIP2PLA2</ci>
<ci>VmaxE2</ci>
<ci>APC</ci>
</apply>
<apply>
<plus/>
<ci>kmE2</ci>
<ci>APC</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>PIP2</ci>
</apply>
<apply>
<minus/>
<apply>
<minus/>
<apply>
<minus/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<ci>CaPLCg</ci>
</apply>
<ci>VmaxF2</ci>
<ci>PIP2</ci>
</apply>
<apply>
<plus/>
<ci>kmF2</ci>
<ci>PIP2</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>CaPLCg_star</ci>
<ci>VmaxF6</ci>
<ci>PIP2</ci>
</apply>
<apply>
<plus/>
<ci>kmF6</ci>
<ci>PIP2</ci>
</apply>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>CaPLC</ci>
<ci>VmaxG7</ci>
<ci>PIP2</ci>
</apply>
<apply>
<plus/>
<ci>kmG7</ci>
<ci>PIP2</ci>
</apply>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>CaGqPLC</ci>
<ci>VmaxG6</ci>
<ci>PIP2</ci>
</apply>
<apply>
<plus/>
<ci>kmG6</ci>
<ci>PIP2</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>DAG</ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<divide/>
<apply>
<times/>
<ci>CaPLCg</ci>
<ci>VmaxF2</ci>
<ci>PIP2</ci>
</apply>
<apply>
<plus/>
<ci>kmF2</ci>
<ci>PIP2</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>CaPLCg_star</ci>
<ci>VmaxF6</ci>
<ci>PIP2</ci>
</apply>
<apply>
<plus/>
<ci>kmF6</ci>
<ci>PIP2</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>CaPLC</ci>
<ci>VmaxG7</ci>
<ci>PIP2</ci>
</apply>
<apply>
<plus/>
<ci>kmG7</ci>
<ci>PIP2</ci>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci>kfG8</ci>
<ci>DAG</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>CaGqPLC</ci>
<ci>VmaxG6</ci>
<ci>PIP2</ci>
</apply>
<apply>
<plus/>
<ci>kmG6</ci>
<ci>PIP2</ci>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci>PKC_i</ci>
<ci>DAG</ci>
<ci>kfK9</ci>
</apply>
</apply>
<apply>
<times/>
<ci>DAGPKC</ci>
<ci>kbK9</ci>
</apply>
</apply>
<apply>
<times/>
<ci>DAG</ci>
<ci>CaPKC</ci>
<ci>kfK8</ci>
</apply>
</apply>
<apply>
<times/>
<ci>DAGCaPKC</ci>
<ci>kbK8</ci>
</apply>
</apply>
<apply>
<times/>
<ci>DAG</ci>
<ci>CaPLA2</ci>
<ci>kfE7</ci>
</apply>
</apply>
<apply>
<times/>
<ci>DAGCaPLA2</ci>
<ci>kbE7</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>IP3</ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<divide/>
<apply>
<times/>
<ci>CaPLCg</ci>
<ci>VmaxF2</ci>
<ci>PIP2</ci>
</apply>
<apply>
<plus/>
<ci>kmF2</ci>
<ci>PIP2</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>CaPLCg_star</ci>
<ci>VmaxF6</ci>
<ci>PIP2</ci>
</apply>
<apply>
<plus/>
<ci>kmF6</ci>
<ci>PIP2</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>CaGqPLC</ci>
<ci>VmaxG6</ci>
<ci>PIP2</ci>
</apply>
<apply>
<plus/>
<ci>kmG6</ci>
<ci>PIP2</ci>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci>kfG9</ci>
<ci>IP3</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>CaPLC</ci>
<ci>VmaxG7</ci>
<ci>PIP2</ci>
</apply>
<apply>
<plus/>
<ci>kmG7</ci>
<ci>PIP2</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>PC</ci>
</apply>
<apply>
<times/>
<ci>kfG8</ci>
<ci>DAG</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>Inositol</ci>
</apply>
<apply>
<times/>
<ci>kfG9</ci>
<ci>IP3</ci>
</apply>
</apply>
</math>
</component>
<connection>
<map_components component_2="environment" component_1="DGBM_Model_Modules"/>
<map_variables variable_2="t" variable_1="t"/>
</connection>
<connection>
<map_components component_2="environment" component_1="KEL_DAGIP3_Model_Modules"/>
<map_variables variable_2="t" variable_1="t"/>
</connection>
<connection>
<map_components component_2="environment" component_1="F_Model_Module_PLC"/>
<map_variables variable_2="t" variable_1="t"/>
</connection>
<connection>
<map_components component_2="environment" component_1="B_Model_Modules"/>
<map_variables variable_2="t" variable_1="t"/>
</connection>
<connection>
<map_components component_2="environment" component_1="H_Model_Module_MAPK"/>
<map_variables variable_2="t" variable_1="t"/>
</connection>
<connection>
<map_components component_2="environment" component_1="H_Model_Module_MAPKK"/>
<map_variables variable_2="t" variable_1="t"/>
</connection>
<connection>
<map_components component_2="environment" component_1="A_Model_Module_EGFR"/>
<map_variables variable_2="t" variable_1="t"/>
</connection>
<connection>
<map_components component_2="environment" component_1="A_Model_Module_SHC"/>
<map_variables variable_2="t" variable_1="t"/>
</connection>
<connection>
<map_components component_2="Calcium" component_1="DGBM_Model_Modules"/>
<map_variables variable_2="Ca" variable_1="Ca"/>
</connection>
<connection>
<map_components component_2="Calcium" component_1="KEL_DAGIP3_Model_Modules"/>
<map_variables variable_2="Ca" variable_1="Ca"/>
</connection>
<connection>
<map_components component_2="Calcium" component_1="F_Model_Module_PLC"/>
<map_variables variable_2="Ca" variable_1="Ca"/>
</connection>
<connection>
<map_components component_2="A_Model_Module_EGFR" component_1="F_Model_Module_PLC"/>
<map_variables variable_2="EGF_EGFR" variable_1="EGF_EGFR"/>
</connection>
<connection>
<map_components component_2="A_Model_Module_SHC" component_1="F_Model_Module_PLC"/>
<map_variables variable_2="CaPLCg" variable_1="CaPLCg"/>
<map_variables variable_2="SHC" variable_1="SHC"/>
</connection>
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