{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:23:43Z","timestamp":1791271423758,"version":"4.1.0"},"reference-count":65,"publisher":"Rockefeller University Press","issue":"11","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1999,12,6]]},"abstract":"<jats:p>The first checkpoint in T cell development occurs between the CD4\u2212CD8\u2212 and CD4+CD8+ stages and is associated with formation of the pre-T cell receptor (TCR). The signaling mechanisms that drive this progression remain largely unknown. Here, we show that extracellular signal\u2013regulated kinases (ERKs)-1\/2 are activated upon engagement of the pre-TCR. Using a novel experimental system, we demonstrate that expression of the pre-TCR by developing thymocytes induces ERK-1\/2 activation within the thymus. In addition, the activation of this pre-TCR signaling cascade is mediated through Lck. These findings directly link pre-TCR complex formation with specific downstream signaling components in vivo.<\/jats:p>","DOI":"10.1084\/jem.190.11.1647","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:48:33Z","timestamp":1027702113000},"page":"1647-1656","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":29,"title":["Extracellular Signal\u2013Regulated Kinase (Erk) Activation by the Pre-T Cell Receptor in Developing Thymocytes in Vivo"],"prefix":"10.1084","volume":"190","author":[{"given":"Alison M.","family":"Michie","sequence":"first","affiliation":[{"name":"aDepartment of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Trop","sequence":"additional","affiliation":[{"name":"aDepartment of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada"},{"name":"bDepartment of Medicine, Division of Experimental Medicine, McGill University, Montr\u00e9al, Qu\u00e9bec H3A 1A3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L.","family":"Wiest","sequence":"additional","affiliation":[{"name":"cDivision of Basic Sciences, Immunobiology Working Group, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Carlos","family":"Z\u00fa\u00f1iga-Pfl\u00fccker","sequence":"additional","affiliation":[{"name":"aDepartment of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[1999,12,6]]},"reference":[{"key":"2023072508453778600_R1","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1146\/annurev.immunol.17.1.829","article-title":"Selection of the T cell repertoire","volume":"17","author":"Sebzda","year":"1999","journal-title":"Annu. Rev. Immunol."},{"key":"2023072508453778600_R2","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1146\/annurev.immunol.14.1.29","article-title":"Early T lymphocyte progenitors","volume":"14","author":"Shortman","year":"1996","journal-title":"Annu. Rev. Immunol."},{"key":"2023072508453778600_R3","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/S0952-7915(96)80060-4","article-title":"Regulation of thymocyte development from immature progenitors","volume":"8","author":"Z\u00fa\u00f1iga-Pfl\u00fccker","year":"1996","journal-title":"Curr. Opin. Immunol."},{"key":"2023072508453778600_R4","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/1074-7613(94)90102-3","article-title":"T cell receptor \u03b2 chain gene rearrangement and selection during thymocyte development in adult mice","volume":"1","author":"Dudley","year":"1994","journal-title":"Immunity."},{"key":"2023072508453778600_R5","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S0952-7915(99)80024-7","article-title":"Pleiotropic changes controlled by the pre-T-cell receptor","volume":"11","author":"von Boehmer","year":"1999","journal-title":"Curr. Opin. Immunol."},{"key":"2023072508453778600_R6","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/1074-7613(95)90056-X","article-title":"Receptors and signals in early thymic selection","volume":"3","author":"Levelt","year":"1995","journal-title":"Immunity."},{"key":"2023072508453778600_R7","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1126\/science.7973703","article-title":"Analysis and expression of a cloned pre-T cell receptor gene","volume":"266","author":"Saint-Ruf","year":"1994","journal-title":"Science."},{"key":"2023072508453778600_R8","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/0167-5699(93)90201-U","article-title":"Role for a pre-T cell receptor in T-cell development","volume":"14","author":"Groettrup","year":"1993","journal-title":"Immunol. Today."},{"key":"2023072508453778600_R9","doi-asserted-by":"crossref","first-page":"2327","DOI":"10.1084\/jem.184.6.2327","article-title":"Proliferation kinetics associated with T cell receptor-\u03b2 chain selection of fetal murine thymocytes","volume":"184","author":"Falk","year":"1996","journal-title":"J. Exp. Med."},{"key":"2023072508453778600_R10","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1101\/gad.10.8.948","article-title":"Productive T-cell receptor \u03b2-chain gene rearrangementcoincident regulation of cell cycle and clonality during development in vivo","volume":"10","author":"Hoffman","year":"1996","journal-title":"Genes Dev."},{"key":"2023072508453778600_R11","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1093\/intimm\/9.10.1475","article-title":"Pre-TCR signalling components trigger transcriptional activation of a rearranged TCR\u03b1 gene locus and silencing of the pre-TCR\u03b1 locusimplications for intrathymic differentiation","volume":"9","author":"Koyasu","year":"1997","journal-title":"Int. Immunol."},{"key":"2023072508453778600_R12","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/S0952-7915(97)80146-X","article-title":"Early \u03b1\u03b2 T cell development in the thymus of normal and genetically altered mice","volume":"9","author":"Fehling","year":"1997","journal-title":"Curr. Opin. Immunol."},{"key":"2023072508453778600_R13","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/0167-5699(95)80096-4","article-title":"A signalling pathway governing early thymocyte maturation","volume":"16","author":"Anderson","year":"1995","journal-title":"Immunol. Today."},{"key":"2023072508453778600_R14","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1084\/jem.179.4.1355","article-title":"Two waves of recombinase gene expression in developing thymocytes","volume":"179","author":"Wilson","year":"1994","journal-title":"J. Exp. Med."},{"key":"2023072508453778600_R15","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1002\/j.1460-2075.1993.tb05812.x","article-title":"A dominant-negative transgene defines a role for p56lck in thymopoiesis","volume":"12","author":"Levin","year":"1993","journal-title":"EMBO (Eur. Mol. Biol. Organ.) J."},{"key":"2023072508453778600_R16","doi-asserted-by":"crossref","first-page":"4641","DOI":"10.1002\/j.1460-2075.1995.tb00146.x","article-title":"Altered T cell development in mice with a targeted mutation of the CD3-\u2208 gene","volume":"14","author":"Malissen","year":"1995","journal-title":"EMBO (Eur. Mol. Biol. Organ.) J."},{"key":"2023072508453778600_R17","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/1074-7613(95)90091-8","article-title":"Regulation of thymocyte development through CD3functional dissociation between p56lck and CD3\u03b6 in early thymic selection","volume":"3","author":"Levelt","year":"1995","journal-title":"Immunity."},{"key":"2023072508453778600_R18","doi-asserted-by":"crossref","first-page":"11401","DOI":"10.1073\/pnas.90.23.11401","article-title":"Restoration of early thymocyte differentiation in T cell receptor \u03b2-chain-deficient mutant mice by transmembrane signalling through CD3\u2208","volume":"90","author":"Levelt","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072508453778600_R19","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1084\/jem.177.3.707","article-title":"Regulation of thymocyte development through CD3. I. Timepoint of ligation of CD3\u2208 determines clonal deletion or induction of developmental program","volume":"177","author":"Levelt","year":"1993","journal-title":"J. Exp. Med."},{"key":"2023072508453778600_R20","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1093\/emboj\/17.7.1871","article-title":"The TCR\u03b3 chain is essential for development of both the TCR\u03b1\u03b2 and TCR\u03b3\u03b4 lineages","volume":"17","author":"Haks","year":"1998","journal-title":"EMBO (Eur. Mol. Biol. Organ.) J."},{"key":"2023072508453778600_R21","doi-asserted-by":"crossref","first-page":"4347","DOI":"10.1002\/j.1460-2075.1993.tb06119.x","article-title":"T cell development in mice lacking the CD3\u03b6\/\u03b7 gene","volume":"12","author":"Malissen","year":"1993","journal-title":"EMBO (Eur. Mol. Biol. Organ.) J."},{"key":"2023072508453778600_R22","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1084\/jem.187.1.105","article-title":"The CD3-\u03b3\u03b4\u2208 and CD3-\u03b6\u03b7 modules are each essential for allelic exclusion at the T cell receptor \u03b2 locus but are both dispensable for the initiation of V to (D)J recombination at the T cell receptor-\u03b2, -\u03b3, and -\u03b4 loci","volume":"187","author":"Ardouin","year":"1998","journal-title":"J. Exp. Med."},{"key":"2023072508453778600_R23","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S0065-2776(08)60018-8","article-title":"Function of the CD3 subunits of the pre-TCR and TCR complexes during T cell development","volume":"72","author":"Malissen","year":"1999","journal-title":"Adv. Immunol."},{"key":"2023072508453778600_R24","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1038\/357161a0","article-title":"Profound block in thymocyte development in mice lacking p56lck","volume":"357","author":"Molina","year":"1992","journal-title":"Nature."},{"key":"2023072508453778600_R25","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/S1074-7613(00)80498-7","article-title":"Fyn can partially substitute for lck in T lymphocyte development","volume":"5","author":"Groves","year":"1996","journal-title":"Immunity."},{"key":"2023072508453778600_R26","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/S1074-7613(00)80499-9","article-title":"\u03b1\u03b2 T cell development is abolished in mice lacking both lck and fyn protein tyrosine kinases","volume":"5","author":"van Oers","year":"1996","journal-title":"Immunity."},{"key":"2023072508453778600_R27","doi-asserted-by":"crossref","first-page":"2888","DOI":"10.4049\/jimmunol.161.6.2888","article-title":"An improved retroviral gene transfer technique demonstrates inhibition of CD4\u2212CD8\u2212 thymocyte development by kinase-inactive ZAP-70","volume":"161","author":"Sugawara","year":"1998","journal-title":"J. Immunol."},{"key":"2023072508453778600_R28","doi-asserted-by":"crossref","first-page":"9797","DOI":"10.1073\/pnas.94.18.9797","article-title":"The syk and ZAP-70 SH2-containing tyrosine kinases are implicated in pre-T cell receptor signalling","volume":"94","author":"Cheng","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072508453778600_R29","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1126\/science.281.5375.416","article-title":"Requirement for the leukocyte-specific adapter protein SLP-76 for normal T cell development","volume":"281","author":"Clements","year":"1998","journal-title":"Science."},{"key":"2023072508453778600_R30","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/S0092-8674(00)81422-1","article-title":"Impaired viability and profound block in thymocyte development in mice lacking the adapter protein SLP-76","volume":"94","author":"Piviouk","year":"1998","journal-title":"Cell."},{"key":"2023072508453778600_R31","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/S1074-7613(00)80032-1","article-title":"Essential role of LAT in T cell development","volume":"10","author":"Zhang","year":"1999","journal-title":"Immunity."},{"key":"2023072508453778600_R32","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1038\/375795a0","article-title":"Crucial role of the pre-T-cell receptor \u03b1 gene in development of \u03b1\u03b2 but not \u03b3\u03b4 T cells","volume":"375","author":"Fehling","year":"1995","journal-title":"Nature."},{"key":"2023072508453778600_R33","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/360225a0","article-title":"Mutations in the T-cell antigen receptor genes \u03b1 and \u03b2 block thymocyte development at different stages","volume":"360","author":"Mombaerts","year":"1992","journal-title":"Nature."},{"key":"2023072508453778600_R34","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/0092-8674(92)90029-C","article-title":"RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement","volume":"68","author":"Shinkai","year":"1992","journal-title":"Cell."},{"key":"2023072508453778600_R35","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/0092-8674(92)90030-G","article-title":"RAG-1-deficient mice have no mature B and T lymphocytes","volume":"68","author":"Mombaerts","year":"1992","journal-title":"Cell."},{"key":"2023072508453778600_R36","doi-asserted-by":"crossref","first-page":"5103","DOI":"10.4049\/jimmunol.154.10.5103","article-title":"Cell expansion and growth arrest phases during the transition from precursor (CD4\u22128\u2212) to immature (CD4+8+) thymocytes in normal and genetically modified mice","volume":"154","author":"P\u00e9nit","year":"1995","journal-title":"J. Immunol."},{"key":"2023072508453778600_R37","doi-asserted-by":"crossref","first-page":"3530","DOI":"10.4049\/jimmunol.151.7.3530","article-title":"Functional and phenotypic analysis of thymocytes in SCID mice. Evidence for functional response transitions before and after the SCID arrest","volume":"151","author":"Rothenberg","year":"1993","journal-title":"J. Immunol."},{"key":"2023072508453778600_R38","doi-asserted-by":"crossref","first-page":"4052","DOI":"10.4049\/jimmunol.158.9.4052","article-title":"Different developmental arrest points in RAG-2\u2212\/\u2212 and SCID thymocytes on two genetic backgrounds. Developmental choices and cell death mechanisms before TCR gene rearrangement","volume":"158","author":"Diamond","year":"1997","journal-title":"J. Immunol."},{"key":"2023072508453778600_R39","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1126\/science.8430336","article-title":"Restoration of T cell development in RAG-2-deficient mice by functional TCR transgenes","volume":"259","author":"Shinkai","year":"1993","journal-title":"Science."},{"key":"2023072508453778600_R40","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1002\/j.1460-2075.1991.tb07924.x","article-title":"Surface expression of the beta T cell receptor (TCR) chain in the absence of other TCR or CD3 proteins on immature T cells","volume":"10","author":"Kishi","year":"1991","journal-title":"EMBO (Eur. Mol. Biol. Organ.) J."},{"key":"2023072508453778600_R41","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/1074-7613(94)90077-9","article-title":"An activated lck transgene promotes thymocyte development in RAG-1 mutant mice","volume":"1","author":"Mombaerts","year":"1994","journal-title":"Immunity."},{"key":"2023072508453778600_R42","doi-asserted-by":"crossref","first-page":"4683","DOI":"10.1073\/pnas.93.10.4683","article-title":"Activated ras signals differentiation and expansion of CD4+CD8+ thymocytes","volume":"93","author":"Swat","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072508453778600_R43","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/S1074-7613(00)80070-9","article-title":"Distinct signals mediate maturation and allelic exclusion in lymphocyte progenitors","volume":"10","author":"Iritani","year":"1999","journal-title":"Immunity."},{"key":"2023072508453778600_R44","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/S0952-7915(99)80040-5","article-title":"T cell antigen-receptor signal transduction","volume":"11","author":"van Leeuwen","year":"1999","journal-title":"Curr. Opin. Immunol."},{"key":"2023072508453778600_R45","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1002\/j.1460-2075.1995.tb07001.x","article-title":"Involvement of p21ras distinguishes positive and negative selection in thymocytes","volume":"14","author":"Swan","year":"1995","journal-title":"EMBO (Eur. Mol. Biol. Organ.) J."},{"key":"2023072508453778600_R46","doi-asserted-by":"crossref","first-page":"2350","DOI":"10.1002\/eji.1830261012","article-title":"Raf regulates positive selection","volume":"26","author":"O'Shea","year":"1996","journal-title":"Eur. J. Immunol."},{"key":"2023072508453778600_R47","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1038\/373620a0","article-title":"Selective requirement for MAP kinase activation in thymocyte differentiation","volume":"373","author":"Alberola-Ila","year":"1995","journal-title":"Nature."},{"key":"2023072508453778600_R48","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1084\/jem.186.9.1461","article-title":"Subunit composition of pre-T cell receptor complexes expressed by primary thymocytesCD3-\u03b4 is physically associated but not functionally required","volume":"186","author":"Berger","year":"1997","journal-title":"J. Exp. Med."},{"key":"2023072508453778600_R49","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.1002\/(SICI)1521-4141(199907)29:07<2187::AID-IMMU2187>3.0.CO;2-D","article-title":"The connecting peptide domain of pT\u03b1 dictates weak association of the pre-T cell receptor with the TCR-\u03b6 subunit","volume":"29","author":"Trop","year":"1999","journal-title":"Eur. J. Immunol."},{"key":"2023072508453778600_R50"},{"key":"2023072508453778600_R51","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.4049\/jimmunol.160.4.1735","article-title":"Early intrathymic precursor cells acquire a CD4(low) phenotype","volume":"160","author":"Michie","year":"1998","journal-title":"J. Immunol."},{"key":"2023072508453778600_R52","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1084\/jem.178.4.1139","article-title":"Gene transcription in differentiating immature T cell receptorneg thymocytes resembles antigen-activated mature T cells","volume":"178","author":"Z\u00fa\u00f1iga-Pfl\u00fccker","year":"1993","journal-title":"J. Exp. Med."},{"key":"2023072508453778600_R53","first-page":"51","article-title":"T-cell differentiation in thymus organ cultures","volume":"2","author":"Jenkinson","year":"1990","journal-title":"Semin. Immunol."},{"key":"2023072508453778600_R54","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/S0092-8674(00)80096-3","article-title":"The MAP kinase pathway controls differentiation from double-negative to double-positive thymocyte","volume":"86","author":"Crompton","year":"1996","journal-title":"Cell."},{"key":"2023072508453778600_R55","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/S1074-7613(00)80446-X","article-title":"Restoration of thymopoiesis in pT\u03b1\u2212\/\u2212 mice by anti-CD3\u2208 antibody treatment or with transgenes encoding activated lck or tailless pT\u03b1","volume":"6","author":"Fehling","year":"1997","journal-title":"Immunity."},{"key":"2023072508453778600_R56","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1006\/cimm.1996.0096","article-title":"Synergy between T cell receptor and Fas (CD95\/APO-1) signaling in mouse thymocyte death","volume":"169","author":"Fisher","year":"1996","journal-title":"Cell. Immunol."},{"key":"2023072508453778600_R57","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S0022-1759(98)00076-3","article-title":"Use of explant technology in the study of in vitro immune responses","volume":"216","author":"Anderson","year":"1998","journal-title":"J. Immunol. Methods."},{"key":"2023072508453778600_R58","first-page":"151","article-title":"Parallel development of the T cell and its receptorimmature forms of the CD3 complex control early thymocyte maturation","volume":"1","author":"Levelt","year":"1993","journal-title":"The Immunologist."},{"key":"2023072508453778600_R59","doi-asserted-by":"crossref","first-page":"5957","DOI":"10.1002\/j.1460-2075.1995.tb00284.x","article-title":"Induction of c-fos expression through JNK-mediated TCF\/Elk-1 phosphorylation","volume":"14","author":"Cavigelli","year":"1995","journal-title":"EMBO (Eur. Mol. Biol. Organ.) J."},{"key":"2023072508453778600_R60","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1128\/MCB.19.1.136","article-title":"Glutamate induces phosphorylation of Elk-1 and CREB, along with c-fos activation, via an extracellular signal-regulated kinase-dependent pathway in brain slices","volume":"19","author":"Vanhoutte","year":"1999","journal-title":"Mol. Cell. Biol."},{"key":"2023072508453778600_R61","doi-asserted-by":"crossref","first-page":"2360","DOI":"10.1128\/MCB.17.5.2360","article-title":"Role of p38 and JNK mitogen-activated protein kinases in the activation of ternary complex factors","volume":"17","author":"Whitmarsh","year":"1997","journal-title":"Mol. Cell. Biol."},{"key":"2023072508453778600_R62","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1093\/intimm\/10.8.1077","article-title":"Analysis of the role of MKK-4\/Sek-1 in T cell development and apoptosis","volume":"10","author":"Alberola-Ila","year":"1998","journal-title":"Int. Immunol."},{"key":"2023072508453778600_R63","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/S0960-9822(99)80065-7","article-title":"JNK2 is required for efficient T-cell activation and apoptosis but not for normal lymphocyte development","volume":"9","author":"Sabapathy","year":"1999","journal-title":"Curr. Biol."},{"key":"2023072508453778600_R64","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/S1074-7613(00)80567-1","article-title":"SEK1\/MKK4 is required for maintenance of a normal peripheral lymphoid compartment but not for lymphocyte development","volume":"8","author":"Swat","year":"1998","journal-title":"Immunity."},{"key":"2023072508453778600_R65","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/S1074-7613(00)80053-9","article-title":"Immature thymocytes employ distinct signaling pathways for allelic exclusion versus differentiation and expansion","volume":"10","author":"G\u00e4rtner","year":"1999","journal-title":"Immunity."}],"container-title":["The Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/190\/11\/1647\/1694383\/99-1462.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/190\/11\/1647\/1694383\/99-1462.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T09:56:48Z","timestamp":1690279008000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/190\/11\/1647\/29938\/Extracellular-Signal-Regulated-Kinase-Erk"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,12,6]]},"references-count":65,"journal-issue":{"issue":"11","published-print":{"date-parts":[[1999,12,6]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.190.11.1647","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,12,6]]}}}