Molecular basis for a direct interaction between the Syk protein-tyrosine kinase and phosphoinositide 3-kinase

摘要: After engagement of the B cell receptor for antigen, Syk protein-tyrosine kinase becomes phosphorylated on multiple tyrosines, some which serve as docking sites downstream effectors with SH2 or other phosphotyrosine binding domains. The most frequently identified partner catalytically active in a yeast two-hybrid screen was p85 regulatory subunit phosphoinositide 3-kinase. C-terminal domain sufficient mediating an interaction tyrosine-phosphorylated Syk. Interestingly, this interacted at 317, site trans by Src family kinase, Lyn, and previously c-Cbl. This preferentially compared c-Cbl tyrosine domain. Molecular modeling studies showed good fit between peptide containing 317. Tyr-317 found to be essential support phagocytosis mediated FcγRIIA receptors expressed heterologous system. These establish new type that can exist proteins substrates kinases provide molecular explanation observations direct interactions