- Author:
- pmr2.import <nobody@models.cellml.org>
- Date:
- 2006-07-09 07:55:18+12:00
- Desc:
- committing version01 of bhalla_iyengar_1999
- Permanent Source URI:
- https://models.physiomeproject.org/workspace/bhalla_iyengar_1999/rawfile/57f524b7908c7ab0980bafc32ae638d65431ea9b/bhalla_iyengar_1999_g.cellml
<?xml version='1.0' encoding='utf-8'?>
<!-- FILE : bi_calcineurin_pathway_1999.xml
CREATED : 7th November 2001
LAST MODIFIED : 9th April 2003
AUTHOR : Catherine Lloyd
Department of Engineering Science
The University of Auckland
MODEL STATUS : This model conforms to the CellML 1.0 Specification released on
10th August 2001, and the 16/01/2002 CellML Metadata 1.0 Specification.
DESCRIPTION : This file contains a CellML description of the calcineurin
pathway model from Bhalla and Iyengar (1999).
CHANGES:
22/01/2002 - AAC - Updated metadata to conform to the 16/1/02 CellML Metadata
1.0 Specification.
18/07/2002 - CML - Added more metadata.
09/04/2003 - AAC - Added publication date information.
--><model xmlns="http://www.cellml.org/cellml/1.0#" xmlns:cmeta="http://www.cellml.org/metadata/1.0#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bqs="http://www.cellml.org/bqs/1.0#" xmlns:cellml="http://www.cellml.org/cellml/1.0#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:pathway_editor="http://www.physiome.com/pathway_editor/1.0#" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" pathway_editor:rendering_config_file="bi calcineurin pathway 1999render.xml" cmeta:id="bhalla_iyengar_1999_version07" name="bhalla_iyengar_1999_version07">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>The Calcineurin (CaN/PP2B) Pathway Model from Bhalla and Iyengar</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Bioengineering Institute, University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<section id="sec_status">
<title>Model Status</title>
<para>
This is the original unchecked version of the model imported from the previous
CellML model repository, 24-Jan-2006.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
In 1999 Upinder S. Bhalla and Ravi Iyengar published a paper discussing the emergent properties of signalling pathway networks. To develop these networks, they modelled individual pathways and compared those results to previously published results before combining the individual pathways to create networks. They only used mechanisms that had already been experimentally described when making connections between pathways. One of the reaction pathways they modelled was the calcineurin (CaN/PP2B) pathway (see <xref linkend="fig_pathway_diagram"/> below).
</para>
<para>
The complete original paper reference is cited below:
</para>
<para>
Emergent properties of networks of biological signaling pathways. Bhalla US, Iyengar R. <ulink url="http://www.sciencemag.org/">
<emphasis>Science</emphasis>
</ulink> 1999 Jan 15; 283(5400); 381-7. (The <ulink url="http://www.sciencemag.org/cgi/content/full/283/5400/381">full text</ulink> of the article is available to members on the <emphasis>Science</emphasis> website.) <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>
<para>
The raw CellML description of the CaN/PP2B pathway 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>
<informalfigure float="0" id="fig_pathway_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>the conventional rendering of the CaN/PP2BC pathway</title>
</objectinfo>
<imagedata fileref="conventional_rendering.gif"/>
</imageobject>
</mediaobject>
<caption>A rendering of the CaN/PP2B pathway. 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>
</sect1>
</article>
</documentation>
<!--
We start the model definition with a definition of some named
sets of units for use throughout the model.
-->
<units name="micromolar">
<unit units="mole" prefix="micro"/>
<unit units="litre" exponent="-1"/>
</units>
<units name="flux">
<unit units="micromolar"/>
<unit units="second" exponent="-1"/>
</units>
<units name="first_order_rate_constant_units">
<unit units="second" exponent="-1"/>
</units>
<units name="second_order_rate_constant_units">
<unit units="micromolar" exponent="-1"/>
<unit units="second" exponent="-1"/>
</units>
<units name="third_order_rate_constant_units">
<unit units="micromolar" exponent="-2"/>
<unit units="second" exponent="-1"/>
</units>
<component name="global_variables">
<variable units="second" public_interface="out" name="time"/>
</component>
<component cmeta:id="PP2B" name="PP2B">
<variable units="micromolar" public_interface="out" name="PP2B"/>
<variable units="flux" public_interface="in" name="delta_PP2B_rxn0"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>PP2B</ci>
</apply>
<ci>delta_PP2B_rxn0</ci>
</apply>
</math>
</component>
<component cmeta:id="Ca" name="Ca">
<variable units="micromolar" public_interface="out" name="Ca" initial_value="1.0"/>
<variable units="flux" public_interface="in" name="delta_Ca_rxn0"/>
<variable units="flux" public_interface="in" name="delta_Ca_rxn1"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca</ci>
</apply>
<apply>
<plus/>
<ci>delta_Ca_rxn0</ci>
<ci>delta_Ca_rxn1</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="Ca2_PP2B" name="Ca2_PP2B">
<variable units="micromolar" public_interface="out" name="Ca2_PP2B"/>
<variable units="flux" public_interface="in" name="delta_Ca2_PP2B_rxn0"/>
<variable units="flux" public_interface="in" name="delta_Ca2_PP2B_rxn1"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca2_PP2B</ci>
</apply>
<apply>
<plus/>
<ci>delta_Ca2_PP2B_rxn0</ci>
<ci>delta_Ca2_PP2B_rxn1</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="Ca4_PP2B" name="Ca4_PP2B">
<variable units="micromolar" public_interface="out" name="Ca4_PP2B" initial_value="1.0"/>
<variable units="flux" public_interface="in" name="delta_Ca4_PP2B_rxn1"/>
<variable units="flux" public_interface="in" name="delta_Ca4_PP2B_rxn2"/>
<variable units="flux" public_interface="in" name="delta_Ca4_PP2B_rxn3"/>
<variable units="flux" public_interface="in" name="delta_Ca4_PP2B_rxn4"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca4_PP2B</ci>
</apply>
<apply>
<plus/>
<ci>delta_Ca4_PP2B_rxn1</ci>
<ci>delta_Ca4_PP2B_rxn2</ci>
<ci>delta_Ca4_PP2B_rxn3</ci>
<ci>delta_Ca4_PP2B_rxn4</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="Ca4_CaM" name="Ca4_CaM">
<variable units="micromolar" public_interface="out" name="Ca4_CaM" initial_value="1.0"/>
<variable units="flux" public_interface="in" name="delta_Ca4_CaM_rxn2"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca4_CaM</ci>
</apply>
<ci>delta_Ca4_CaM_rxn2</ci>
</apply>
</math>
</component>
<component cmeta:id="Ca4_CaM_Ca4_PP2B" name="Ca4_CaM_Ca4_PP2B">
<variable units="micromolar" public_interface="out" name="Ca4_CaM_Ca4_PP2B"/>
<variable units="flux" public_interface="in" name="delta_Ca4_CaM_Ca4_PP2B_rxn2"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca4_CaM_Ca4_PP2B</ci>
</apply>
<ci>delta_Ca4_CaM_Ca4_PP2B_rxn2</ci>
</apply>
</math>
</component>
<component cmeta:id="Ca3_CaM" name="Ca3_CaM">
<variable units="micromolar" public_interface="out" name="Ca3_CaM" initial_value="1.0"/>
<variable units="flux" public_interface="in" name="delta_Ca3_CaM_rxn3"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca3_CaM</ci>
</apply>
<ci>delta_Ca3_CaM_rxn3</ci>
</apply>
</math>
</component>
<component cmeta:id="Ca3_CaM_Ca4_PP2B" name="Ca3_CaM_Ca4_PP2B">
<variable units="micromolar" public_interface="out" name="Ca3_CaM_Ca4_PP2B" initial_value="1.0"/>
<variable units="flux" public_interface="in" name="delta_Ca3_CaM_Ca4_PP2B_rxn3"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca3_CaM_Ca4_PP2B</ci>
</apply>
<ci>delta_Ca3_CaM_Ca4_PP2B_rxn3</ci>
</apply>
</math>
</component>
<component cmeta:id="Ca2_CaM" name="Ca2_CaM">
<variable units="micromolar" public_interface="out" name="Ca2_CaM" initial_value="1.0"/>
<variable units="flux" public_interface="in" name="delta_Ca2_CaM_rxn4"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca2_CaM</ci>
</apply>
<ci>delta_Ca2_CaM_rxn4</ci>
</apply>
</math>
</component>
<component cmeta:id="Ca2_CaM_Ca4_PP2B" name="Ca2_CaM_Ca4_PP2B">
<variable units="micromolar" public_interface="out" name="Ca2_CaM_Ca4_PP2B" initial_value="1.0"/>
<variable units="flux" public_interface="in" name="delta_Ca2_CaM_Ca4_PP2B_rxn4"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca2_CaM_Ca4_PP2B</ci>
</apply>
<ci>delta_Ca2_CaM_Ca4_PP2B_rxn4</ci>
</apply>
</math>
</component>
<component name="reaction0">
<variable units="micromolar" public_interface="in" name="PP2B"/>
<variable units="micromolar" public_interface="in" name="Ca"/>
<variable units="micromolar" public_interface="in" name="Ca2_PP2B"/>
<variable units="flux" public_interface="out" name="delta_PP2B_rxn0"/>
<variable units="flux" public_interface="out" name="delta_Ca_rxn0"/>
<variable units="flux" public_interface="out" name="delta_Ca2_PP2B_rxn0"/>
<variable units="third_order_rate_constant_units" name="k0" initial_value="0.0000000278"/>
<variable units="first_order_rate_constant_units" name="k0_" initial_value="1.0"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="PP2B">
<role stoichiometry="1" direction="forward" delta_variable="delta_PP2B_rxn0" role="reactant"/>
</variable_ref>
<variable_ref variable="Ca">
<role stoichiometry="2" direction="forward" delta_variable="delta_Ca_rxn0" role="reactant"/>
</variable_ref>
<variable_ref variable="Ca2_PP2B">
<role stoichiometry="1" direction="forward" delta_variable="delta_Ca2_PP2B_rxn0" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k0</ci>
<ci>PP2B</ci>
<apply>
<power/>
<ci>Ca</ci>
<cn cellml:units="flux">2.0</cn>
</apply>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k0_</ci>
<ci>Ca2_PP2B</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction1">
<variable units="micromolar" public_interface="in" name="Ca"/>
<variable units="micromolar" public_interface="in" name="Ca2_PP2B"/>
<variable units="micromolar" public_interface="in" name="Ca4_PP2B"/>
<variable units="flux" public_interface="out" name="delta_Ca_rxn1"/>
<variable units="flux" public_interface="out" name="delta_Ca2_PP2B_rxn1"/>
<variable units="flux" public_interface="out" name="delta_Ca4_PP2B_rxn1"/>
<variable units="third_order_rate_constant_units" name="k1" initial_value="0.00000000001"/>
<variable units="first_order_rate_constant_units" name="k1_" initial_value="1.0"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="Ca">
<role stoichiometry="2" direction="forward" delta_variable="delta_Ca_rxn1" role="reactant"/>
</variable_ref>
<variable_ref variable="Ca2_PP2B">
<role stoichiometry="1" direction="forward" delta_variable="delta_Ca2_PP2B_rxn1" role="reactant"/>
</variable_ref>
<variable_ref variable="Ca4_PP2B">
<role stoichiometry="1" direction="forward" delta_variable="delta_Ca4_PP2B_rxn1" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k1</ci>
<apply>
<power/>
<ci>Ca</ci>
<cn cellml:units="flux">2.0</cn>
</apply>
<ci>Ca2_PP2B</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k1_</ci>
<ci>Ca4_PP2B</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction2">
<variable units="micromolar" public_interface="in" name="Ca4_CaM"/>
<variable units="micromolar" public_interface="in" name="Ca4_PP2B"/>
<variable units="micromolar" public_interface="in" name="Ca4_CaM_Ca4_PP2B"/>
<variable units="flux" public_interface="out" name="delta_Ca4_CaM_rxn2"/>
<variable units="flux" public_interface="out" name="delta_Ca4_PP2B_rxn2"/>
<variable units="flux" public_interface="out" name="delta_Ca4_CaM_Ca4_PP2B_rxn2"/>
<variable units="second_order_rate_constant_units" name="k2" initial_value="0.0010"/>
<variable units="first_order_rate_constant_units" name="k2_" initial_value="1.0"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="Ca4_CaM">
<role stoichiometry="1" direction="forward" delta_variable="delta_Ca4_CaM_rxn2" role="reactant"/>
</variable_ref>
<variable_ref variable="Ca4_PP2B">
<role stoichiometry="1" direction="forward" delta_variable="delta_Ca4_PP2B_rxn2" role="reactant"/>
</variable_ref>
<variable_ref variable="Ca4_CaM_Ca4_PP2B">
<role stoichiometry="1" direction="forward" delta_variable="delta_Ca4_CaM_Ca4_PP2B_rxn2" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k2</ci>
<ci>Ca4_CaM</ci>
<ci>Ca4_PP2B</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k2_</ci>
<ci>Ca4_CaM_Ca4_PP2B</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction3">
<variable units="micromolar" public_interface="in" name="Ca4_PP2B"/>
<variable units="micromolar" public_interface="in" name="Ca3_CaM"/>
<variable units="micromolar" public_interface="in" name="Ca3_CaM_Ca4_PP2B"/>
<variable units="flux" public_interface="out" name="delta_Ca4_PP2B_rxn3"/>
<variable units="flux" public_interface="out" name="delta_Ca3_CaM_rxn3"/>
<variable units="flux" public_interface="out" name="delta_Ca3_CaM_Ca4_PP2B_rxn3"/>
<variable units="second_order_rate_constant_units" name="k3" initial_value="0.00000373"/>
<variable units="first_order_rate_constant_units" name="k3_" initial_value="1.0"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="Ca4_PP2B">
<role stoichiometry="1" direction="forward" delta_variable="delta_Ca4_PP2B_rxn3" role="reactant"/>
</variable_ref>
<variable_ref variable="Ca3_CaM">
<role stoichiometry="1" direction="forward" delta_variable="delta_Ca3_CaM_rxn3" role="reactant"/>
</variable_ref>
<variable_ref variable="Ca3_CaM_Ca4_PP2B">
<role stoichiometry="1" direction="forward" delta_variable="delta_Ca3_CaM_Ca4_PP2B_rxn3" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k3</ci>
<ci>Ca4_PP2B</ci>
<ci>Ca3_CaM</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k3_</ci>
<ci>Ca3_CaM_Ca4_PP2B</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction4">
<variable units="micromolar" public_interface="in" name="Ca4_PP2B"/>
<variable units="micromolar" public_interface="in" name="Ca2_CaM"/>
<variable units="micromolar" public_interface="in" name="Ca2_CaM_Ca4_PP2B"/>
<variable units="flux" public_interface="out" name="delta_Ca4_PP2B_rxn4"/>
<variable units="flux" public_interface="out" name="delta_Ca2_CaM_rxn4"/>
<variable units="flux" public_interface="out" name="delta_Ca2_CaM_Ca4_PP2B_rxn4"/>
<variable units="second_order_rate_constant_units" name="k4" initial_value="0.0000004"/>
<variable units="first_order_rate_constant_units" name="k4_" initial_value="1.0"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="Ca4_PP2B">
<role stoichiometry="1" direction="forward" delta_variable="delta_Ca4_PP2B_rxn4" role="reactant"/>
</variable_ref>
<variable_ref variable="Ca2_CaM">
<role stoichiometry="1" direction="forward" delta_variable="delta_Ca2_CaM_rxn4" role="reactant"/>
</variable_ref>
<variable_ref variable="Ca2_CaM_Ca4_PP2B">
<role stoichiometry="1" direction="forward" delta_variable="delta_Ca2_CaM_Ca4_PP2B_rxn4" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k4</ci>
<ci>Ca4_PP2B</ci>
<ci>Ca2_CaM</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k4_</ci>
<ci>Ca2_CaM_Ca4_PP2B</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<connection>
<map_components component_2="reaction0" component_1="PP2B"/>
<map_variables variable_2="PP2B" variable_1="PP2B"/>
<map_variables variable_2="delta_PP2B_rxn0" variable_1="delta_PP2B_rxn0"/>
</connection>
<connection>
<map_components component_2="reaction0" component_1="Ca"/>
<map_variables variable_2="Ca" variable_1="Ca"/>
<map_variables variable_2="delta_Ca_rxn0" variable_1="delta_Ca_rxn0"/>
</connection>
<connection>
<map_components component_2="reaction1" component_1="Ca"/>
<map_variables variable_2="Ca" variable_1="Ca"/>
<map_variables variable_2="delta_Ca_rxn1" variable_1="delta_Ca_rxn1"/>
</connection>
<connection>
<map_components component_2="reaction0" component_1="Ca2_PP2B"/>
<map_variables variable_2="Ca2_PP2B" variable_1="Ca2_PP2B"/>
<map_variables variable_2="delta_Ca2_PP2B_rxn0" variable_1="delta_Ca2_PP2B_rxn0"/>
</connection>
<connection>
<map_components component_2="reaction1" component_1="Ca2_PP2B"/>
<map_variables variable_2="Ca2_PP2B" variable_1="Ca2_PP2B"/>
<map_variables variable_2="delta_Ca2_PP2B_rxn1" variable_1="delta_Ca2_PP2B_rxn1"/>
</connection>
<connection>
<map_components component_2="reaction1" component_1="Ca4_PP2B"/>
<map_variables variable_2="Ca4_PP2B" variable_1="Ca4_PP2B"/>
<map_variables variable_2="delta_Ca4_PP2B_rxn1" variable_1="delta_Ca4_PP2B_rxn1"/>
</connection>
<connection>
<map_components component_2="reaction2" component_1="Ca4_PP2B"/>
<map_variables variable_2="Ca4_PP2B" variable_1="Ca4_PP2B"/>
<map_variables variable_2="delta_Ca4_PP2B_rxn2" variable_1="delta_Ca4_PP2B_rxn2"/>
</connection>
<connection>
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calcium-calmodulin-calcineurin complex
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Emergent Properties of Networks of Biological Signaling Pathways
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