Uncoupling of nonreceptor tyrosine kinases from PLC-gamma1 in an SLP-76-deficient T cell.
Activation of nonreceptor protein tyrosine kinases (PTKs) is essential for T cell receptor (TCR) responsiveness; however, the function of individual PTK substrates is often uncertain. A mutant T cell line was isolated that lacked expression of SLP-76 (SH2 domain-containing leukocyte protein of 76 kilodaltons), a hematopoietically expressed adaptor protein and PTK substrate. SLP-76 was not required for TCR-induced tyrosine phosphorylation of most proteins, but was required for optimal tyrosine phosphorylation and activation of phospholipase C-gamma1 (PLC-gamma1), as well as Ras pathway activation. TCR-inducible gene expression was dependent on SLP-76. Thus, coupling of TCR-regulated PTKs to downstream signaling pathways requires SLP-76.
Department of Medicine, Howard Hughes Medical Institute, Box 0795, University of California, San Francisco, San Francisco, CA 94143-0795, USA.
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Yablonski
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Kuhne
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Kadlecek
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Weiss
D048868:Adaptor Proteins, Signal Transducing; D002118:Calcium / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D007376:Interleukin-2 / Q000235:genetics; D007527:Isoenzymes / Q000378:metabolism*; D019169:Jurkat Cells; D008565:Membrane Proteins; D019950:Mitogen-Activated Protein Kinase 1; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D051966:Phospholipase C gamma; D010750:Phosphoproteins / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000201:enzymology / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection; D010738:Type C Phospholipases / Q000378:metabolism*; D018631:ras Proteins / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D007295:Inositol Phosphates; D007376:Interleukin-2; D007527:Isoenzymes; C110810:LAT protein, human; D008565:Membrane Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011948:Receptors, Antigen, T-Cell; C092947:SLP-76 signal Transducing adaptor proteins; D014157:Transcription Factors; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D018631:ras Proteins; D002118:Calcium