title: Grap negatively regulates T-cell receptor-elicited lymphocyte proliferation and interleukin-2 induction.
abstract: Grb-2-related adaptor protein (Grap) is a Grb2-like SH3-SH2-SH3 adaptor protein with expression restricted to lymphoid tissues. Grap(-/-) lymphocytes isolated from targeted Grap-deficient mice exhibited enhanced proliferation, interleukin-2 production, and c-fos induction in response to mitogenic T-cell receptor (TCR) stimulation, compared to wild-type cells. Ectopic expression of Grap led to a suppression of Elk-1-directed transcription induced by the Ras/Erk pathway, without having effects on gene expression mediated by Jnk and p38 mitogen-activated protein kinases. Together, these data suggest that Grap, unlike Grb2, acts as a negative regulator of TCR-stimulated intracellular signaling by downregulating signal relay through the Ras/Erk pathway.
authors.affiliation: Program in Signal Transduction Research, The Burnham Institute, La Jolla, California 92037, USA.
authors.forename: Randy
authors.initials: R
authors.lastname: Shen
authors.forename: Ying-Bin
authors.initials: YB
authors.lastname: Ouyang
authors.forename: Cheng-Kui
authors.initials: CK
authors.lastname: Qu
authors.forename: Andres
authors.initials: A
authors.lastname: Alonso
authors.forename: Lindsey
authors.initials: L
authors.lastname: Sperzel
authors.forename: Tomas
authors.initials: T
authors.lastname: Mustelin
authors.forename: Mark H
authors.initials: MH
authors.lastname: Kaplan
authors.forename: Gen-Sheng
authors.initials: GS
authors.lastname: Feng
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004268:DNA-Binding Proteins; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D007376:Interleukin-2 / Q000378:metabolism*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D018631:ras Proteins / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C494113:Elk1 protein, mouse; D007376:Interleukin-2; C498726:Mona protein, mouse; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D011948:Receptors, Antigen, T-Cell; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins