{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T19:39:43Z","timestamp":1790105983382,"version":"4.0.1"},"reference-count":24,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2015,6,5]],"date-time":"2015-06-05T00:00:00Z","timestamp":1433462400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["intramural research program"],"award-info":[{"award-number":["intramural research program"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2015,8]]},"abstract":"<jats:p>Sos\u20101 and Sos\u20102 are ubiquitously expressed Ras\u2010guanine exchange factors involved in Erk\u2010MAP kinase pathway activation. Using mice lacking genes encoding Sos\u20101 and Sos\u20102, we evaluated the role of these proteins in peripheral T\u2010cell signaling and function. Our results confirmed that TCR\u2010mediated Erk activation in peripheral CD4<jats:sup>+<\/jats:sup> T\u00a0cells does not depend on Sos\u20101 and Sos\u20102, although IL\u20102\u2010mediated Erk activation does. Unexpectedly, however, we show an increase in AKT phosphorylation in Sos\u20101\/2dKO CD4<jats:sup>+<\/jats:sup> T\u00a0cells upon TCR and IL\u20102 stimulation. Activation of AKT was likely a consequence of increased recruitment of PI3K to Grb2 upon TCR and\/or IL\u20102 stimulation in Sos\u20101\/2dKO CD4<jats:sup>+<\/jats:sup> T\u00a0cells. The increased activity of the PI3K\/AKT pathway led to downregulation of the surface receptor CD62L in Sos\u20101\/2dKO T\u00a0cells and a subsequent impairment in T\u2010cell migration.<\/jats:p>","DOI":"10.1002\/eji.201445226","type":"journal-article","created":{"date-parts":[[2015,5,14]],"date-time":"2015-05-14T10:27:53Z","timestamp":1431599273000},"page":"2389-2395","source":"Crossref","is-referenced-by-count":23,"title":["Absence of both Sos\u20101 and Sos\u20102 in peripheral CD4<sup>+<\/sup> T\u00a0cells leads to PI3K pathway activation and defects in migration"],"prefix":"10.1002","volume":"45","author":[{"given":"Geoffrey","family":"Guittard","sequence":"first","affiliation":[{"name":"Laboratory of Cellular and Molecular Biology Center for Cancer Research, National Cancer Institute  Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert L.","family":"Kortum","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Biology Center for Cancer Research, National Cancer Institute  Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lakshmi","family":"Balagopalan","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Biology Center for Cancer Research, National Cancer Institute  Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"\u00c7uburu","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Oncology Center for Cancer Research, National Cancer Institute  Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phan","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Biology Center for Cancer Research, National Cancer Institute  Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connie L.","family":"Sommers","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Biology Center for Cancer Research, National Cancer Institute  Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence E.","family":"Samelson","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Biology Center for Cancer Research, National Cancer Institute  Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,6,5]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2013.00239"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2013.02.004"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/1947601911408078"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a005512"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb1133"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2004494"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1104295108"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00317-12"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201344046"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01882-06"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2012.17"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2012.08.011"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00750.x"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90146-H"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1905"},{"key":"e_1_2_7_17_1","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1016\/S0021-9258(17)42115-6","article-title":"Identification of two SH3\u2010binding motifs in the regulatory subunit of phosphatidylinositol 3\u2010kinase","volume":"269","author":"Kapeller R.","year":"1994","journal-title":"J. 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