Src family protein tyrosine kinase (SFK)

The Src family protein tyrosine kinases (SFKs) are a group of non-receptor tyrosine kinases consisting of nine closely related proteins in humans: Src, Yes, Fyn, Fgr, Lck, Hck, Blk, Lyn, and Frk. SFKs share a conserved domain structure with an N-terminal myristoylation region critical for membrane association, an SH3 and SH2 domain for protein-protein interactions, a kinase (SH1) domain, and a C-terminal regulatory tail. They mediate phosphorylation of tyrosine residues on various target proteins and play crucial roles in signal transduction pathways regulating cell proliferation, differentiation, migration, adhesion, survival, and immune responses. Aberrant SFK activation—due to overexpression, constitutive activation, or loss of regulatory control—is implicated in cancer and other pathologies. SFKs are established therapeutic targets, with several small molecule inhibitors in clinical use or development. Despite overlapping and redundant functions, their essential roles in signaling and disease make them important molecular targets for both oncology and non-oncology indications.

Other names

Src kinasesSrc family kinaseSFKSrc tyrosine kinasesNon-receptor tyrosine kinase familySrc, Yes, Fyn, Fgr, Lck, Hck, Blk, Lyn, Frk (individual family members)

Inhibition of kinase activity by blocking the ATP binding site of SFKs, preventing phosphorylation of downstream substrates; Dual inhibition (some drugs inhibit additional kinases, e.g., Bcr-Abl/Src dual inhibitors); Destabilization or degradation of the protein (e.g., HSP90 inhibitors affect SFK stability); Interference with protein-protein interactions within signaling complexes.