title: TCR-mediated Erk activation does not depend on Sos and Grb2 in peripheral human T cells.
abstract: Sos proteins are ubiquitously expressed activators of Ras. Lymphoid cells also express RasGRP1, another Ras activator. Sos and RasGRP1 are thought to cooperatively control full Ras activation upon T-cell receptor triggering. Using RNA interference, we evaluated whether this mechanism operates in primary human T cells. We found that T-cell antigen receptor (TCR)-mediated Erk activation requires RasGRP1, but not Grb2/Sos. Conversely, Grb2/Sos—but not RasGRP1—are required for IL2-mediated Erk activation. Thus, RasGRP1 and Grb2/Sos are insulators of signals that lead to Ras activation induced by different stimuli, rather than cooperating downstream of the TCR.
authors.affiliation: Institute of Molecular and Clinical Immunology, Otto-von-Guericke University, Leipziger Strasse 44, Magdeburg 39120, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Warnecke
authors.forename: Mateusz
authors.initials: M
authors.lastname: Poltorak
authors.forename: Bhavani S
authors.initials: BS
authors.lastname: Kowtharapu
authors.forename: Boerge
authors.initials: B
authors.lastname: Arndt
authors.forename: James C
authors.initials: JC
authors.lastname: Stone
authors.forename: Burkhart
authors.initials: B
authors.lastname: Schraven
authors.forename: Luca
authors.initials: L
authors.lastname: Simeoni
mesh_terms: D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D051380:GRB2 Adaptor Protein / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D034741:RNA, Small Interfering / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D020839:Son of Sevenless Protein, Drosophila / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology
chemical_list: D004268:DNA-Binding Proteins; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; D020662:Guanine Nucleotide Exchange Factors; D007376:Interleukin-2; C491790:RASGRP1 protein, human; D034741:RNA, Small Interfering; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D020839:Son of Sevenless Protein, Drosophila; D048049:Extracellular Signal-Regulated MAP Kinases