Src family tyrosine-protein kinase (SFK) (SFK)

The Src family tyrosine kinases (SFKs) are a group of non-receptor protein tyrosine kinases that play a fundamental role in regulating diverse cellular processes, including growth, differentiation, adhesion, and migration (PMID: 15184870). This family consists of nine members in humans: Src, Fyn, Yes, Blk, Yrk, Fgr, Hck, Lck, and Lyn, which share a conserved structure comprising SH1 (catalytic), SH2, SH3, and SH4 domains (UniProt: P12931). SFKs act as critical signaling hubs, integrating signals from various cell surface receptors such as G protein-coupled receptors, integrins, and receptor tyrosine kinases (PMID: 24832465). Dysregulation or overexpression of SFKs is frequently observed in numerous malignancies, where they contribute to tumor progression, epithelial-to-mesenchymal transition, and metastasis (PMID: 18441416). Consequently, SFKs have become significant therapeutic targets in oncology, leading to the development of several small-molecule inhibitors (StatPearls: NBK537231). While drugs like dasatinib and bosutinib are clinically approved for leukemia, their multi-kinase inhibitory profiles often lead to off-target effects and safety concerns like pleural effusion (PMID: 20660295). Ongoing research continues to explore the potential of SFK inhibitors in solid tumors and inflammatory conditions (PMID: 24832465).

Other names

Src family kinasesSFKsNon-receptor tyrosine kinases of the Src familyProto-oncogene tyrosine-protein kinase Src family

ATP-competitive inhibition of the catalytic kinase domain, preventing the phosphorylation of downstream substrates and inhibiting signaling pathways such as Ras/MAPK and PI3K/Akt (PMID: 15184870).