Cbl functions downstream of Src kinases in FCγRI signaling in primary human macrophages

摘要: Cbl is a cytosolic protein that rapidly tyrosine phosphorylated in response to Fc receptor activation and binds the adaptor proteins Grb2, CrkL, Nck. A few reports describe interactions primary human hematopoietic cells. We show evidence participates signaling initiated by gammaRI cross-linking macrophages, functions downstream of Src family kinases this pathway. stimulation macrophages was associated with rapid transient phosphorylation protein. Immunoprecipitated complexed several proteins, most prominent which 38-kDa band identified as CrkL tyrosine-phosphorylated itself became after cross-linking. SLP-76, recently cloned Grb2-associated protein, strongly both Grb2. Grb2 binding SLP-76 were inducible macrophages. Nck inducibly bound stimulation, whereas constitutively it. Shc also PP1, specific inhibitor kinases, inhibited gammaRI-induced respiratory burst, well its association CrkL. These results suggest fundamental role for Cbl, Experiments performed kinase inhibitor, demonstrate first Cbl-Crkl interaction are targets myeloid required NADPH oxidase activity.