Modeling species-specific diacylglycerol dynamics in the RAW 264.7 macrophage
A mathematical model of the G protein signaling pathway in RAW 264.7 macrophages downstream of P 2 Y 6 receptors activated by the ubiquitous signaling nucleotide uridine 5 ’-diphosphate is developed. The model, which is based on time-course measurements of inositol trisphosphate, cytosolic calcium,...
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| Veröffentlicht in: | Journal of theoretical biology 2010-02, Vol.262 (4), p.679-690 |
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| container_title | Journal of theoretical biology |
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| creator | Callender, Hannah L. Horn, Mary Ann DeCamp, Dianne L. Sternweis, Paul C. Alex Brown, H. |
| description | A mathematical model of the G protein signaling pathway in RAW 264.7 macrophages downstream of
P
2
Y
6
receptors activated by the ubiquitous signaling nucleotide uridine
5
’-diphosphate
is developed. The model, which is based on time-course measurements of inositol trisphosphate, cytosolic calcium, and diacylglycerol, focuses particularly on differential dynamics of multiple chemical species of diacylglycerol. When using the canonical pathway representation, the model predicted that key interactions were missing from the current network structure. Indeed, the model suggested that accurate depiction of experimental observations required an additional branch to the signaling pathway. An intracellular pool of diacylglycerol is immediately phosphorylated upon stimulation of an extracellular receptor for uridine
5
’-diphosphate
and subsequently used to aid replenishment of phosphatidylinositol. As a result of sensitivity analysis of the model parameters, key predictions can be made regarding which of these parameters are the most sensitive to perturbations and are therefore most responsible for output uncertainty. |
| doi_str_mv | 10.1016/j.jtbi.2009.10.030 |
| format | Article |
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P
2
Y
6
receptors activated by the ubiquitous signaling nucleotide uridine
5
’-diphosphate
is developed. The model, which is based on time-course measurements of inositol trisphosphate, cytosolic calcium, and diacylglycerol, focuses particularly on differential dynamics of multiple chemical species of diacylglycerol. When using the canonical pathway representation, the model predicted that key interactions were missing from the current network structure. Indeed, the model suggested that accurate depiction of experimental observations required an additional branch to the signaling pathway. An intracellular pool of diacylglycerol is immediately phosphorylated upon stimulation of an extracellular receptor for uridine
5
’-diphosphate
and subsequently used to aid replenishment of phosphatidylinositol. As a result of sensitivity analysis of the model parameters, key predictions can be made regarding which of these parameters are the most sensitive to perturbations and are therefore most responsible for output uncertainty.</description><identifier>ISSN: 0022-5193</identifier><identifier>EISSN: 1095-8541</identifier><identifier>DOI: 10.1016/j.jtbi.2009.10.030</identifier><identifier>PMID: 19883664</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>[formula omitted] receptor ; Animals ; Calcium - metabolism ; Cellular signaling pathways ; Computer Simulation ; Cytosol - metabolism ; Diglycerides - pharmacology ; GTP-Binding Proteins - metabolism ; Hydrolysis ; Macrophages - cytology ; Macrophages - metabolism ; Mathematical modeling ; Mice ; Models, Biological ; Models, Theoretical ; Phosphorylation ; Receptors, Purinergic P2 - metabolism ; Sensitivity analysis ; Signal Transduction ; Uridine [formula omitted] ; Uridine Diphosphate - chemistry</subject><ispartof>Journal of theoretical biology, 2010-02, Vol.262 (4), p.679-690</ispartof><rights>2009 Elsevier Ltd</rights><rights>(c) 2009 Elsevier Ltd. All rights reserved.</rights><rights>2009 Elsevier Ltd. All rights reserved. 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c486t-e6f5446b8c932a01b0914044ec38cbff492124e02fd9e248b57a7cb2db893a033</citedby><cites>FETCH-LOGICAL-c486t-e6f5446b8c932a01b0914044ec38cbff492124e02fd9e248b57a7cb2db893a033</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0022519309005190$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19883664$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Callender, Hannah L.</creatorcontrib><creatorcontrib>Horn, Mary Ann</creatorcontrib><creatorcontrib>DeCamp, Dianne L.</creatorcontrib><creatorcontrib>Sternweis, Paul C.</creatorcontrib><creatorcontrib>Alex Brown, H.</creatorcontrib><title>Modeling species-specific diacylglycerol dynamics in the RAW 264.7 macrophage</title><title>Journal of theoretical biology</title><addtitle>J Theor Biol</addtitle><description>A mathematical model of the G protein signaling pathway in RAW 264.7 macrophages downstream of
P
2
Y
6
receptors activated by the ubiquitous signaling nucleotide uridine
5
’-diphosphate
is developed. The model, which is based on time-course measurements of inositol trisphosphate, cytosolic calcium, and diacylglycerol, focuses particularly on differential dynamics of multiple chemical species of diacylglycerol. When using the canonical pathway representation, the model predicted that key interactions were missing from the current network structure. Indeed, the model suggested that accurate depiction of experimental observations required an additional branch to the signaling pathway. An intracellular pool of diacylglycerol is immediately phosphorylated upon stimulation of an extracellular receptor for uridine
5
’-diphosphate
and subsequently used to aid replenishment of phosphatidylinositol. As a result of sensitivity analysis of the model parameters, key predictions can be made regarding which of these parameters are the most sensitive to perturbations and are therefore most responsible for output uncertainty.</description><subject>[formula omitted] receptor</subject><subject>Animals</subject><subject>Calcium - metabolism</subject><subject>Cellular signaling pathways</subject><subject>Computer Simulation</subject><subject>Cytosol - metabolism</subject><subject>Diglycerides - pharmacology</subject><subject>GTP-Binding Proteins - metabolism</subject><subject>Hydrolysis</subject><subject>Macrophages - cytology</subject><subject>Macrophages - metabolism</subject><subject>Mathematical modeling</subject><subject>Mice</subject><subject>Models, Biological</subject><subject>Models, Theoretical</subject><subject>Phosphorylation</subject><subject>Receptors, Purinergic P2 - metabolism</subject><subject>Sensitivity analysis</subject><subject>Signal Transduction</subject><subject>Uridine [formula omitted]</subject><subject>Uridine Diphosphate - chemistry</subject><issn>0022-5193</issn><issn>1095-8541</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1rGzEQhkVJSZw0f6CHsLecdjv6WK0EoRBM0hQSCiElR6HVztoy--FK64D_feXapO0lOQ2MnnnRzEPIZwoFBSq_rIrVVPuCAejUKIDDBzKjoMtclYIekRkAY3lJNT8hpzGuIIGCy2NyQrVSXEoxIw8PY4OdHxZZXKPzGPM_tfUua7x1227RbR2Gscua7WB772Lmh2xaYvZ4_ZwxKYoq660L43ppF_iJfGxtF_H8UM_Iz9ubp_ldfv_j2_f59X3uhJJTjrIthZC1cpozC7QGTQUIgY4rV7et0IwygcDaRiMTqi4rW7maNbXS3ALnZ-TrPne9qXtsHA5TsJ1ZB9_bsDWj9eb_l8EvzWJ8MUwxRnmZAi4PAWH8tcE4md5Hh11nBxw30aiqKqWCUr9LVpxTRbVgiWR7Ml0jxoDt638omJ0wszI7YWYnbNdLwtLQxb-b_B05GErA1R7AdM8Xj8HEpGlw2PiAbjLN6N_K_w2d76b_</recordid><startdate>20100221</startdate><enddate>20100221</enddate><creator>Callender, Hannah L.</creator><creator>Horn, Mary Ann</creator><creator>DeCamp, Dianne L.</creator><creator>Sternweis, Paul C.</creator><creator>Alex Brown, H.</creator><general>Elsevier Ltd</general><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><scope>7QP</scope><scope>7T5</scope><scope>H94</scope><scope>5PM</scope></search><sort><creationdate>20100221</creationdate><title>Modeling species-specific diacylglycerol dynamics in the RAW 264.7 macrophage</title><author>Callender, Hannah L. ; Horn, Mary Ann ; DeCamp, Dianne L. ; Sternweis, Paul C. ; Alex Brown, H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c486t-e6f5446b8c932a01b0914044ec38cbff492124e02fd9e248b57a7cb2db893a033</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>[formula omitted] receptor</topic><topic>Animals</topic><topic>Calcium - metabolism</topic><topic>Cellular signaling pathways</topic><topic>Computer Simulation</topic><topic>Cytosol - metabolism</topic><topic>Diglycerides - pharmacology</topic><topic>GTP-Binding Proteins - metabolism</topic><topic>Hydrolysis</topic><topic>Macrophages - cytology</topic><topic>Macrophages - metabolism</topic><topic>Mathematical modeling</topic><topic>Mice</topic><topic>Models, Biological</topic><topic>Models, Theoretical</topic><topic>Phosphorylation</topic><topic>Receptors, Purinergic P2 - metabolism</topic><topic>Sensitivity analysis</topic><topic>Signal Transduction</topic><topic>Uridine [formula omitted]</topic><topic>Uridine Diphosphate - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Callender, Hannah L.</creatorcontrib><creatorcontrib>Horn, Mary Ann</creatorcontrib><creatorcontrib>DeCamp, Dianne L.</creatorcontrib><creatorcontrib>Sternweis, Paul C.</creatorcontrib><creatorcontrib>Alex Brown, H.</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><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of theoretical biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Callender, Hannah L.</au><au>Horn, Mary Ann</au><au>DeCamp, Dianne L.</au><au>Sternweis, Paul C.</au><au>Alex Brown, H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Modeling species-specific diacylglycerol dynamics in the RAW 264.7 macrophage</atitle><jtitle>Journal of theoretical biology</jtitle><addtitle>J Theor Biol</addtitle><date>2010-02-21</date><risdate>2010</risdate><volume>262</volume><issue>4</issue><spage>679</spage><epage>690</epage><pages>679-690</pages><issn>0022-5193</issn><eissn>1095-8541</eissn><abstract>A mathematical model of the G protein signaling pathway in RAW 264.7 macrophages downstream of
P
2
Y
6
receptors activated by the ubiquitous signaling nucleotide uridine
5
’-diphosphate
is developed. The model, which is based on time-course measurements of inositol trisphosphate, cytosolic calcium, and diacylglycerol, focuses particularly on differential dynamics of multiple chemical species of diacylglycerol. When using the canonical pathway representation, the model predicted that key interactions were missing from the current network structure. Indeed, the model suggested that accurate depiction of experimental observations required an additional branch to the signaling pathway. An intracellular pool of diacylglycerol is immediately phosphorylated upon stimulation of an extracellular receptor for uridine
5
’-diphosphate
and subsequently used to aid replenishment of phosphatidylinositol. As a result of sensitivity analysis of the model parameters, key predictions can be made regarding which of these parameters are the most sensitive to perturbations and are therefore most responsible for output uncertainty.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>19883664</pmid><doi>10.1016/j.jtbi.2009.10.030</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-5193 |
| ispartof | Journal of theoretical biology, 2010-02, Vol.262 (4), p.679-690 |
| issn | 0022-5193 1095-8541 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2822135 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | [formula omitted] receptor Animals Calcium - metabolism Cellular signaling pathways Computer Simulation Cytosol - metabolism Diglycerides - pharmacology GTP-Binding Proteins - metabolism Hydrolysis Macrophages - cytology Macrophages - metabolism Mathematical modeling Mice Models, Biological Models, Theoretical Phosphorylation Receptors, Purinergic P2 - metabolism Sensitivity analysis Signal Transduction Uridine [formula omitted] Uridine Diphosphate - chemistry |
| title | Modeling species-specific diacylglycerol dynamics in the RAW 264.7 macrophage |
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