The product of the proto-oncogene c-cbl: a negative regulator of the Syk tyrosine kinase.
Engagement of antigen and immunoglobulin receptors on hematopoietic cells is directly coupled to activation of nonreceptor protein tyrosine kinases (PTKs) that then phosphorylate critical intracellular substrates. In mast cells stimulated through the FcvarepsilonRI receptor, activation of several PTKs including Syk leads to degranulation and release of such mediators of the allergic response as histamine and serotonin. Regulation of Syk function occurred through interaction with the Cbl protein, itself a PTK substrate in this system. Overexpression of Cbl led to inhibition of Syk and suppression of serotonin release from mast cells, demonstrating its ability to inhibit a nonreceptor tyrosine kinase. Complex adaptor proteins such as Cbl can directly regulate the functions of the proteins they bind.
Ota
Y
Y
Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-5430, USA.
Samelson
L E
LE
D000818:Animals; D015550:Cell Degranulation; D004792:Enzyme Precursors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005822:Genetic Vectors; D047908:Intracellular Signaling Peptides and Proteins; D008407:Mast Cells / Q000378:metabolism*; D009154:Mutation; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D050721:Proto-Oncogene Proteins c-cbl; D051381:Rats; D017455:Receptors, IgE / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D015398:Signal Transduction; D000072377:Syk Kinase; D014407:Tumor Cells, Cultured; D044767:Ubiquitin-Protein Ligases; D014616:Vaccinia virus
D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D017455:Receptors, IgE; D017452:Receptors, IgG; D011994:Recombinant Proteins; D019000:Phosphotyrosine; D012701:Serotonin; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606898:Syk protein, rat; C067419:CBL protein, human