A theoretical approach to G-protein modulation of cellular responsiveness
Structure and function of cells often depend critically on molecular signals arriving at their surface. There are universal mechanisms of signal transduction and signal processing across cell membranes. In this paper the mechanisms involving guanine-nucleotide regulatory proteins ("G-proteins&q...
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Veröffentlicht in: | Journal of mathematical biology 1997-05, Vol.35 (5), p.609-627 |
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description | Structure and function of cells often depend critically on molecular signals arriving at their surface. There are universal mechanisms of signal transduction and signal processing across cell membranes. In this paper the mechanisms involving guanine-nucleotide regulatory proteins ("G-proteins") and certain receptor-kinases are considered. On the basis of recent findings in molecular biology a mathematical model is developed taking into account all essential components in the biochemical network between first and second messenger. There are two coupled feedback loops inherent in this process. The model finally consists of three nonlinear equations, which are obtained from a system of originally ten equations by using conservation laws and quasi-steady state conditions. The second part of the paper contains a mathematical analysis of the model. Solutions describing the temporal development of the involved biochemical species are shown to be bounded, more specifically to remain, independent of the size of the input signal, in a bounded domain of the state space. For the situation of stationary input signals existence, uniqueness and asymptotic stability of steady states are derived. We also demonstrate biologically relevant stimulus-response properties like monotonicity and saturation effects. For temporally non-constant input signals we show numerically that the model is able to produce phenomena of hypersensitivity and desensitization which are important characteristics of cellular responsiveness. |
doi_str_mv | 10.1007/s002850050068 |
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There are universal mechanisms of signal transduction and signal processing across cell membranes. In this paper the mechanisms involving guanine-nucleotide regulatory proteins ("G-proteins") and certain receptor-kinases are considered. On the basis of recent findings in molecular biology a mathematical model is developed taking into account all essential components in the biochemical network between first and second messenger. There are two coupled feedback loops inherent in this process. The model finally consists of three nonlinear equations, which are obtained from a system of originally ten equations by using conservation laws and quasi-steady state conditions. The second part of the paper contains a mathematical analysis of the model. Solutions describing the temporal development of the involved biochemical species are shown to be bounded, more specifically to remain, independent of the size of the input signal, in a bounded domain of the state space. For the situation of stationary input signals existence, uniqueness and asymptotic stability of steady states are derived. We also demonstrate biologically relevant stimulus-response properties like monotonicity and saturation effects. 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There are universal mechanisms of signal transduction and signal processing across cell membranes. In this paper the mechanisms involving guanine-nucleotide regulatory proteins ("G-proteins") and certain receptor-kinases are considered. On the basis of recent findings in molecular biology a mathematical model is developed taking into account all essential components in the biochemical network between first and second messenger. There are two coupled feedback loops inherent in this process. The model finally consists of three nonlinear equations, which are obtained from a system of originally ten equations by using conservation laws and quasi-steady state conditions. The second part of the paper contains a mathematical analysis of the model. Solutions describing the temporal development of the involved biochemical species are shown to be bounded, more specifically to remain, independent of the size of the input signal, in a bounded domain of the state space. For the situation of stationary input signals existence, uniqueness and asymptotic stability of steady states are derived. We also demonstrate biologically relevant stimulus-response properties like monotonicity and saturation effects. For temporally non-constant input signals we show numerically that the model is able to produce phenomena of hypersensitivity and desensitization which are important characteristics of cellular responsiveness.</description><subject>Animals</subject><subject>Cell Membrane - physiology</subject><subject>Feedback</subject><subject>GTP-Binding Proteins - physiology</subject><subject>Humans</subject><subject>Mathematics</subject><subject>Models, Biological</subject><subject>Nonlinear Dynamics</subject><subject>Signal Transduction - physiology</subject><issn>0303-6812</issn><issn>1432-1416</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkEFLxDAQRoMo67p69Cjk5C06aZomOS6i68KCFz2XNJ2ylbapSSv4782yiyAMzAw8hm8eIbccHjiAeowAmZYAqQp9RpY8FxnjOS_OyRIECFZonl2Sqxg_AbiShi_IwvBcGimXZLum0x59wKl1tqN2HIO3bk8nTzcszRO2A-19PXd2av1AfUMddl1aAw0YRz_E9hsHjPGaXDS2i3hz6ivy8fL8_vTKdm-b7dN6x1ym9cQKUWCBpm4McAO5rJTUhVRcK8wc8LoygGBQ1Vqr9B7WmWxcU0PKXolcWrEi98e7Kd3XjHEq-zYeMtkB_RxLZZIIxVUC2RF0wccYsCnH0PY2_JQcyoO68p-6xN-dDs9Vj_UffXIlfgFLFGh5</recordid><startdate>19970501</startdate><enddate>19970501</enddate><creator>Nauroschat, J</creator><creator>an der Heiden, U</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>19970501</creationdate><title>A theoretical approach to G-protein modulation of cellular responsiveness</title><author>Nauroschat, J ; an der Heiden, U</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c288t-636e6e9df9019045b758657187e2c01db90e09e7d887007ed25fcfd0001b345a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>Animals</topic><topic>Cell Membrane - physiology</topic><topic>Feedback</topic><topic>GTP-Binding Proteins - physiology</topic><topic>Humans</topic><topic>Mathematics</topic><topic>Models, Biological</topic><topic>Nonlinear Dynamics</topic><topic>Signal Transduction - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nauroschat, J</creatorcontrib><creatorcontrib>an der Heiden, U</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of mathematical biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nauroschat, J</au><au>an der Heiden, U</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A theoretical approach to G-protein modulation of cellular responsiveness</atitle><jtitle>Journal of mathematical biology</jtitle><addtitle>J Math Biol</addtitle><date>1997-05-01</date><risdate>1997</risdate><volume>35</volume><issue>5</issue><spage>609</spage><epage>627</epage><pages>609-627</pages><issn>0303-6812</issn><eissn>1432-1416</eissn><abstract>Structure and function of cells often depend critically on molecular signals arriving at their surface. 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For the situation of stationary input signals existence, uniqueness and asymptotic stability of steady states are derived. We also demonstrate biologically relevant stimulus-response properties like monotonicity and saturation effects. For temporally non-constant input signals we show numerically that the model is able to produce phenomena of hypersensitivity and desensitization which are important characteristics of cellular responsiveness.</abstract><cop>Germany</cop><pmid>9145955</pmid><doi>10.1007/s002850050068</doi><tpages>19</tpages></addata></record> |
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subjects | Animals Cell Membrane - physiology Feedback GTP-Binding Proteins - physiology Humans Mathematics Models, Biological Nonlinear Dynamics Signal Transduction - physiology |
title | A theoretical approach to G-protein modulation of cellular responsiveness |
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