Binding of NCK to SOS and activation of ras-dependent gene expression.
NCK, an SH2- and SH3 domain-containing protein, becomes phosphorylated and associated with tyrosine kinase receptors upon growth factor stimulation. The sequence of NCK suggests that NCK functions as a linker between receptors and a downstream signaling molecule. To determine if NCK can mediate growth factor-stimulated responses, we measured the ability of NCK to activate the fos promoter. We found that in NIH 3T3 cells, NCK strongly activates this promoter. The effect of NCK on the fos promoter is enhanced by c-ras and blocked by dominant negative ras. We also found that NCK binds directly to the guanine nucleotide exchange factor SOS. This interaction is mediated by the SH3 domains of NCK. These findings suggest that NCK can regulate p21ras-dependent gene transcription through interaction with SOS protein.
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Daiichi Research Center, Cardiovascular Research Institute, University of California at San Francisco 94143.
Milfay
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Williams
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D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D018076:DNA, Complementary; D005786:Gene Expression Regulation; D016762:Genes, fos; D011905:Genes, ras; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute; D008565:Membrane Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D020664:Son of Sevenless Proteins; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D048868:Adaptor Proteins, Signal Transducing; D018076:DNA, Complementary; D008565:Membrane Proteins; C078332:Nck protein; D015513:Oncogene Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D020664:Son of Sevenless Proteins; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)