{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T08:42:31Z","timestamp":1793090551784,"version":"4.5.0"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI165381"],"award-info":[{"award-number":["R01 AI165381"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["P01 AI091580"],"award-info":[{"award-number":["P01 AI091580"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Ras guanine nucleotide-releasing protein 1 (Rasgrp1) is a Ras guanine nucleotide exchange factor that participates in the activation of the Ras\u2013ERK signaling pathway in developing T cells and is required for efficient thymic T cell positive selection. However, the role of Rasgrp1 in mature peripheral T cells has not been definitively addressed, in part because peripheral T cells from constitutive Rasgrp1-deficient mice show an abnormal activated phenotype. In this study, we generated an inducible Rasgrp1-deficient mouse model to allow acute disruption of Rasgrp1 in peripheral CD4+ T cells in the context of normal T cell development. TCR\/CD28-mediated activation of Ras\u2013ERK signaling was blocked in Rasgrp1-deficient peripheral CD4+ T cells. Furthermore, Rasgrp1-deficient CD4+ T cells were unable to synthesize IL-2 and the high-affinity IL-2R and were unable to proliferate in response to TCR\/CD28 stimulation. These findings highlight an essential function for Rasgrp1 for TCR\/CD28-induced Ras\u2013ERK activation in peripheral CD4+ T cells.<\/jats:p>","DOI":"10.4049\/jimmunol.2300138","type":"journal-article","created":{"date-parts":[[2023,8,11]],"date-time":"2023-08-11T16:20:54Z","timestamp":1691770854000},"page":"917-922","source":"Crossref","is-referenced-by-count":8,"title":["Cutting Edge: Induced Loss of Rasgrp1 in Peripheral CD4+ T Cells of Conditional Rasgrp1-Deficient Mice Reveals an Essential Role for Rasgrp1 in TCR\/CD28-Induced Ras\u2013MAPK Signaling"],"prefix":"10.1093","volume":"211","author":[{"given":"Yating","family":"Chang","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Michigan Medical School , Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2679-8626","authenticated-orcid":false,"given":"Praveen","family":"Manivannan","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Michigan Medical School , Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8052-5963","authenticated-orcid":false,"given":"Abbas","family":"Doosti","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Michigan Medical School , Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip E","family":"Lapinski","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Michigan Medical School , Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9509-2814","authenticated-orcid":false,"given":"Di","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Michigan Medical School , Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4746-2811","authenticated-orcid":false,"given":"Jeroen P","family":"Roose","sequence":"additional","affiliation":[{"name":"Department of Anatomy, University of California, San Francisco , San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5598-2748","authenticated-orcid":false,"given":"Philip D","family":"King","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Michigan Medical School , Ann Arbor, MI"},{"name":"Department of Anatomy, University of California, San Francisco , San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,9,15]]},"reference":[{"key":"2025020406114602400_r1","first-page":"178","article-title":"Many faces of Ras activation","volume":"1786","author":"Buday","year":"2008","journal-title":"Biochim. 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