{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T15:24:28Z","timestamp":1782141868079,"version":"3.54.5"},"reference-count":51,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2007,8,24]],"date-time":"2007-08-24T00:00:00Z","timestamp":1187913600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.0030163","type":"journal-article","created":{"date-parts":[[2007,8,22]],"date-time":"2007-08-22T14:58:40Z","timestamp":1187794720000},"page":"e163","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":292,"title":["A Logical Model Provides Insights into T Cell Receptor Signaling"],"prefix":"10.1371","volume":"3","author":[{"given":"Julio","family":"Saez-Rodriguez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Simeoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan A","family":"Lindquist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Hemenway","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ursula","family":"Bommhardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boerge","family":"Arndt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Utz-Uwe","family":"Haus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Weismantel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernst D","family":"Gilles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Klamt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burkhart","family":"Schraven","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2007,8,24]]},"reference":[{"key":"pcbi-0030163-b001","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1038\/nature01254","article-title":"Computational systems biology.","volume":"420","year":"2002","journal-title":"Nature"},{"key":"pcbi-0030163-b002","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/16483","article-title":"Robustness in bacterial chemotaxis.","volume":"397","year":"1999","journal-title":"Nature"},{"key":"pcbi-0030163-b003","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S0962-8924(02)00009-0","article-title":"Computational modeling of the EGF-receptor system: A paradigm for systems biology.","volume":"13","year":"2003","journal-title":"Trends Cell Biol"},{"key":"pcbi-0030163-b004","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/ncb1233","article-title":"Prediction and validation of the distinct dynamics of transient and sustained ERK activation.","volume":"7","year":"2005","journal-title":"Nat Cell Biol"},{"key":"pcbi-0030163-b005","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1371\/journal.pbio.0030356","article-title":"Modeling T cell antigen discrimination based on feedback control of digital ERK responses.","volume":"3","year":"2005","journal-title":"PLoS Biol"},{"key":"pcbi-0030163-b006","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/nrm1570","article-title":"Reconstruction of cellular signalling networks and analysis of their properties.","volume":"6","year":"2005","journal-title":"Nat Rev Mol Cell Biol"},{"key":"pcbi-0030163-b007","doi-asserted-by":"crossref","unstructured":"OdaKMatsuokaYFunahashiAKitanoH\n\t\t\t\t\t2005\n\t\t\t\t\tA comprehensive pathway map of epidermal growth factor receptor signaling.\n\t\t\t\t\tMol Syst Biol\n\t\t\t\t\tdoi:10.1038\/msb4100014","DOI":"10.1038\/msb4100014"},{"key":"pcbi-0030163-b008","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/35075138","article-title":"Lethality and centrality in protein networks.","volume":"411","year":"2001","journal-title":"Nature"},{"key":"pcbi-0030163-b009","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1126\/science.298.5594.824","article-title":"Network motifs: Simple building blocks of complex networks.","volume":"298","year":"2002","journal-title":"Science"},{"key":"pcbi-0030163-b010","doi-asserted-by":"crossref","unstructured":"Ma'ayanAJenkinsSLNevesSHasseldineAGraceE\n\t\t\t\t\tFormation of regulatory patterns during signal propagation in a Mammalian cellular network.\n\t\t\t\t\tScience\n\t\t\t\t\t309\n\t\t\t\t\t1078\n\t\t\t\t\t1083","DOI":"10.1126\/science.1108876"},{"key":"pcbi-0030163-b011","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1038\/nature01166","article-title":"Metabolic network structure determines key aspects of functionality and regulation.","volume":"420","year":"2002","journal-title":"Nature"},{"key":"pcbi-0030163-b012","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1038\/nrmicro1023","article-title":"Genome-scale models of microbial cells: Evaluating the consequences of constraints.","volume":"2","year":"2004","journal-title":"Nat Rev Microbiol"},{"key":"pcbi-0030163-b013","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/1471-2105-7-56","article-title":"A methodology for the structural and functional analysis of signaling and regulatory networks.","volume":"7","year":"2006","journal-title":"BMC Bioinformatics"},{"key":"pcbi-0030163-b014","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/0022-5193(69)90015-0","article-title":"Metabolic stability and epigenesis in randomly constructed genetic nets.","volume":"22","year":"1969","journal-title":"J Theor Biol"},{"key":"pcbi-0030163-b015","unstructured":"ThomasRD'AriR\n\t\t\t\t\t1990\n\t\t\t\t\tBiological feedback\n\t\t\t\t\tBoca Raton (Florida)\n\t\t\t\t\tCRC Press"},{"key":"pcbi-0030163-b016","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1093\/bioinformatics\/15.7.593","article-title":"Genetic control of flower morphogenesis in Arabidopsis thaliana: A logical analysis.","volume":"15","year":"1999","journal-title":"Bioinformatics"},{"key":"pcbi-0030163-b017","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0022-5193(03)00035-3","article-title":"The topology of the regulatory interactions predicts the expression pattern of the Drosophila segment polarity genes.","volume":"223","year":"2003","journal-title":"J Theor Biology"},{"key":"pcbi-0030163-b018","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.jtbi.2005.01.023","article-title":"Robustness and fragility of Boolean models for genetic regulatory networks.","volume":"235","year":"2005","journal-title":"J Theor Biol"},{"key":"pcbi-0030163-b019","unstructured":"BenjaminiECoicoRSunshineG\n\t\t\t\t\t2000\n\t\t\t\t\tImmunology\u2014A short course\n\t\t\t\t\tNew York\n\t\t\t\t\tWiley-Liss"},{"key":"pcbi-0030163-b020","doi-asserted-by":"crossref","first-page":"28827","DOI":"10.1074\/jbc.R400012200","article-title":"T cell receptor signaling: Beyond complex complexes.","volume":"279","year":"2004","journal-title":"J Biol Chem"},{"key":"pcbi-0030163-b021","first-page":"1539","article-title":"T cell receptor signaling precedes immunological synapse formation.","volume":"295","year":"2003","journal-title":"Science"},{"key":"pcbi-0030163-b022","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1098\/rspb.2003.2587","article-title":"Feedback control of T-cell receptor activation.","volume":"271","year":"2004","journal-title":"Proc Biol Sci"},{"key":"pcbi-0030163-b023","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.biosystems.2005.10.004","article-title":"A network model for the control of the differentiation process in Th cells.","volume":"84","year":"2006","journal-title":"Biosystems"},{"key":"pcbi-0030163-b024","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1038\/18050","article-title":"Structure of the amino-terminal domain of Cbl complexed to its binding site on ZAP-70 kinase.","volume":"398","year":"1999","journal-title":"Nature"},{"key":"pcbi-0030163-b025","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.immuni.2004.06.012","article-title":"The Cbl family and other ubiquitin ligases destructive forces in control of antigen receptor signaling.","volume":"21","year":"2004","journal-title":"Immunity"},{"key":"pcbi-0030163-b026","first-page":"153","article-title":"c-Cbl and Cbl-b ubiquitin ligases: Substrate diversity and the negative regulation of signalling responses.","volume":"15","year":"2005","journal-title":"Biochem J"},{"key":"pcbi-0030163-b027","first-page":"44","article-title":"Bow ties, metabolism and disease.","volume":"22","year":"2004","journal-title":"Trends Biotechnol"},{"key":"pcbi-0030163-b028","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/nri1335","article-title":"Feedback regulation of lymphocyte signalling.","volume":"4","year":"2004","journal-title":"Nat Rev Immunol"},{"key":"pcbi-0030163-b029","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1006\/jtbi.2002.2544","article-title":"Positive and negative feedback: Striking a balance between necessary antagonists.","volume":"216","year":"2002","journal-title":"J Theor Biol"},{"key":"pcbi-0030163-b030","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/11905455_8","article-title":"On differentiation and homeostatic behaviours of Boolean dynamical systems.","volume":"4230","year":"2006","journal-title":"Lect Notes Comput Sci"},{"key":"pcbi-0030163-b031","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1752-0509-1-2","article-title":"Structural and functional analysis of cellular networks with CellNetAnalyzer.","volume":"1","year":"2007","journal-title":"BMC Systems Biology"},{"key":"pcbi-0030163-b032","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/1074-7613(95)90171-X","article-title":"CD28pYMNM mutations implicate phosphatidylinositol 3-kinase in CD86-CD28-mediated costimulation.","volume":"3","year":"1995","journal-title":"Immunity"},{"key":"pcbi-0030163-b033","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1034\/j.1600-065X.2003.00005.x","article-title":"Independent CD28 signaling via VAV and SLP-76: A model for in trans costimulation.","volume":"192","year":"2003","journal-title":"Immunol Rev"},{"key":"pcbi-0030163-b034","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/0092-8674(94)90056-6","article-title":"JNK is involved in signal integration during costimulation of T lymphocytes.","volume":"77","year":"1994","journal-title":"Cell"},{"key":"pcbi-0030163-b035","doi-asserted-by":"crossref","first-page":"2451","DOI":"10.4049\/jimmunol.169.5.2451","article-title":"TCR-Independent CD30 signaling selectively induces IL-13 production via a TNF receptor-associated factor\/p38 mitogen-activated protein kinase-dependent mechanism.","volume":"169","year":"2002","journal-title":"J Immunol"},{"key":"pcbi-0030163-b036","doi-asserted-by":"crossref","first-page":"2208","DOI":"10.1002\/(SICI)1521-4141(199807)28:07<2208::AID-IMMU2208>3.0.CO;2-L","article-title":"The TNF receptor family member CD27 signals to Jun N-terminal kinase via Traf-2.","volume":"28","year":"1998","journal-title":"Eur J Immunology"},{"key":"pcbi-0030163-b037","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1074\/jbc.271.2.695","article-title":"Discovery of a novel, potent, and Src family-selective tyrosine kinase inhibitor. Study of Lck- and FynT-dependent T cell activation.","volume":"271","year":"1996","journal-title":"J Biol Chem"},{"key":"pcbi-0030163-b038","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1084\/jem.190.3.375","article-title":"Proline residues in CD28 and the Src homology (SH)3 domain of Lck are required for T cell costimulation.","volume":"190","year":"1999","journal-title":"J Exp Med"},{"key":"pcbi-0030163-b039","doi-asserted-by":"crossref","first-page":"7848","DOI":"10.4049\/jimmunol.175.12.7848","article-title":"Ligation of CD28 by its natural ligand CD86 in the absence of TCR stimulation induces lipid raft polarization in human CD4 T cells.","volume":"175","year":"2005","journal-title":"J Immunol"},{"key":"pcbi-0030163-b040","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.coi.2005.04.003","article-title":"Vav-family proteins in T-cell signalling.","volume":"17","year":"2005","journal-title":"Curr Opin Immunol"},{"key":"pcbi-0030163-b041","doi-asserted-by":"crossref","first-page":"2364","DOI":"10.1128\/MCB.25.6.2364-2383.2005","article-title":"Activation of hematopoietic progenitor kinase 1 involves relocation, autophosphorylation, and transphosphorylation by protein kinase D1.","volume":"25","year":"2005","journal-title":"Mol Cell Biol"},{"key":"pcbi-0030163-b042","doi-asserted-by":"crossref","first-page":"18160","DOI":"10.1074\/jbc.275.24.18160","article-title":"Tyrosine-phosphorylated Vav1 as a point of integration for T-cell receptor- and CD28-mediated activation of JNK, p38, and interleukin-2 transcription.","volume":"275","year":"2000","journal-title":"J Biol Chem"},{"key":"pcbi-0030163-b043","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1038\/sj.leu.2403762","article-title":"T-cell ZAP-70 overexpression in chronic lymphocytic leukemia (CLL) correlates with CLL cell ZAP-70 levels, clinical stage and disease progression.","volume":"19","year":"2005","journal-title":"Leukemia"},{"key":"pcbi-0030163-b044","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1038\/sj.leu.2402824","article-title":"Involvement of PI3K\/Akt pathway in cell cycle progression, apoptosis, and neoplastic transformation: A target for cancer chemotherapy.","volume":"17","year":"2003","journal-title":"Leukemia"},{"key":"pcbi-0030163-b045","doi-asserted-by":"crossref","unstructured":"Bentires-AljMGilSGChanRWangZCWangY\n\t\t\t\t\tA role for the scaffolding adapter GAB2 in breast cancer.\n\t\t\t\t\tNat Med\n\t\t\t\t\t12\n\t\t\t\t\t114\n\t\t\t\t\t121","DOI":"10.1038\/nm1341"},{"key":"pcbi-0030163-b046","first-page":"2643","article-title":"Expression of phospholipase C-gamma 1 and its transcriptional regulators in breast cancer tissues.","volume":"18","year":"1998","journal-title":"Anticancer Res"},{"key":"pcbi-0030163-b047","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.cell.2004.09.008","article-title":"Robustness of cellular functions.","volume":"118","year":"2004","journal-title":"Cell"},{"key":"pcbi-0030163-b048","unstructured":"SchrijverA\n\t\t\t\t\t2003\n\t\t\t\t\tCombinatorial optimization\n\t\t\t\t\tBerlin\n\t\t\t\t\tSpringer"},{"key":"pcbi-0030163-b049","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1126\/science.281.5375.413","article-title":"Uncoupling of nonreceptor tyrosine kinases from PLC-gamma1 in an SLP-76-deficient T cell.","volume":"281","year":"1998","journal-title":"Science"},{"key":"pcbi-0030163-b050","doi-asserted-by":"crossref","first-page":"14859","DOI":"10.1073\/pnas.0406168101","article-title":"Activation of naive CD4 T cells by anti-CD3 reveals an important role for Fyn in Lck-mediated signaling.","volume":"101","year":"2004","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pcbi-0030163-b051","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1126\/science.284.5414.638","article-title":"Requirement for Tec kinases Rlk and Itk in T cell receptor signaling and immunity.","volume":"284","year":"1999","journal-title":"Science"}],"container-title":["PLoS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.0030163","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,6]],"date-time":"2020-05-06T22:19:44Z","timestamp":1588803584000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.0030163"}},"subtitle":[],"editor":[{"given":"Rob J","family":"De Boer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2007,8,24]]},"references-count":51,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2007,8,24]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.0030163","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,8,24]]}}}