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In this reverse genetic study, we show that the MAPK Erk2 is not essential for T cell proliferation in the presence of optimum costimulation. Instead, it has opposite effects on T-bet and Gata3 expression and, hence, on Th1 and Th2 differentiation. Alternatively, in the presence of TGF-\u03b2, the Erk pathway suppresses a large program of gene expression, effectively limiting the differentiation of Foxp3+ regulatory T cells. In the latter case, the mechanisms involved include suppression of Gata3 and Foxp3, induction of Tbx21, phosphorylation of Smad2,3, and possibly suppression of Socs2, a positive inducer of Stat5 signaling. Consequently, loss of Erk2 severely impeded Th1 differentiation while enhancing the development of Foxp3+-induced T regulatory cells. Selected profiles of gene expression under multiple conditions of T cell activation illustrate the opposing consequences of Erk pathway signaling.<\/jats:p>","DOI":"10.4049\/jimmunol.1103015","type":"journal-article","created":{"date-parts":[[2012,6,6]],"date-time":"2012-06-06T22:50:39Z","timestamp":1339023039000},"page":"721-731","source":"Crossref","is-referenced-by-count":85,"title":["Polar Opposites: Erk Direction of CD4 T Cell Subsets"],"prefix":"10.1093","volume":"189","author":[{"given":"Chiung-Fang","family":"Chang","sequence":"first","affiliation":[{"name":"University of California , San Diego, La Jolla, CA 92093-0377"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warren N","family":"D\u2019Souza","sequence":"additional","affiliation":[{"name":"Amgen Inc. , Thousand Oaks, CA 91320"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene L","family":"Ch\u2019en","sequence":"additional","affiliation":[{"name":"University of California , San Diego, La Jolla, CA 92093-0377"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Pages","sequence":"additional","affiliation":[{"name":"Institute of Developmental Biology and Cancer Research, University of Nice Sophia-Antipolis, Centre National de la Recherche Scientifique, Unit\u00e9 Mixte de Recherche 6543, Antoine Lacassagne Center , 06189 Nice,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Pouyssegur","sequence":"additional","affiliation":[{"name":"Institute of Developmental Biology and Cancer Research, University of Nice Sophia-Antipolis, Centre National de la Recherche Scientifique, Unit\u00e9 Mixte de Recherche 6543, Antoine Lacassagne Center , 06189 Nice,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen M","family":"Hedrick","sequence":"additional","affiliation":[{"name":"University of California , San Diego, La Jolla, CA 92093-0377"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,7,15]]},"reference":[{"key":"2025032409210301400_r1","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1111\/j.1600-065X.2010.00951.x","article-title":"Peripheral CD4+ T-cell differentiation regulated by networks of cytokines and transcription factors","volume":"238","author":"Zhu","year":"2010","journal-title":"Immunol. 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