Src family kinase (SFK)

Src family kinases are a group of non-receptor protein tyrosine kinases comprising at least nine closely related enzymes in humans—Src, Yes, Fyn, Fgr (“SrcA” subfamily); Lck, Hck, Blk (“SrcB” subfamily); Lyn; plus Frk/Brk/Srm-related proteins. They share a conserved structure featuring an N-terminal myristoylation site for membrane localization followed by SH3/SH2 domains mediating protein interactions and a C-terminal regulatory tail. These enzymes play central roles in cellular signal transduction by phosphorylating key substrates on tyrosine residues following engagement by various receptors—including growth factor receptors and immune receptors. Their functions span regulation of proliferation, differentiation, motility/migration/adhesion processes as well as critical roles within the immune system’s T cells and B cells. Dysregulation—such as constitutive activation or overexpression—is implicated in oncogenic transformation/progression across many cancers. Accordingly they are considered important therapeutic targets especially within oncology but also inflammatory diseases and organ injury contexts.

Other names

Src family kinasesSFKsNon-receptor tyrosine kinases (when referring to this specific family)Proto-oncogene tyrosine-protein kinase Src familyProtein tyrosine kinase, Src family

Drugs targeting Src family kinases typically act as ATP competitive inhibitors of the catalytic domain, blocking phosphorylation of downstream substrates. This inhibits signal transduction pathways involved in proliferation, survival, migration, angiogenesis, and immune cell activation.