Grap negatively regulates T-cell receptor-elicited lymphocyte proliferation and interleukin-2 induction.
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.
Shen
Randy
R
Program in Signal Transduction Research, The Burnham Institute, La Jolla, California 92037, USA.
Ouyang
Ying-Bin
YB
Qu
Cheng-Kui
CK
Alonso
Andres
A
Sperzel
Lindsey
L
Mustelin
Tomas
T
Kaplan
Mark H
MH
Feng
Gen-Sheng
GS
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
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