Src-family kinases (SFKs) (SFKs)

Src-family kinases (SFKs) are a group of non-receptor tyrosine kinases that serve as critical mediators in various intracellular signaling pathways (Source: UniProt). In macrophages, the family is primarily represented by Hematopoietic cell kinase (Hck), Gardner-Rasheed feline sarcoma viral oncogene homolog (Fgr), and Lck/Yes-related novel tyrosine kinase (Lyn) (Source: PubMed: 17541433). These kinases are essential for regulating myeloid-specific functions, including phagocytosis, chemotaxis, and the release of pro-inflammatory cytokines (Source: Journal of Leukocyte Biology). Dysregulation of macrophage SFKs is strongly linked to the progression of chronic inflammatory diseases, such as rheumatoid arthritis, and the maintenance of an immunosuppressive tumor microenvironment (Source: Nature Reviews Cancer). Small-molecule inhibitors like dasatinib and saracatinib target the ATP-binding site of these kinases to modulate their activity in clinical settings (Source: Clinical Cancer Research). While effective, the high structural conservation among SFK members often leads to off-target effects and safety concerns such as myelosuppression (Source: PubMed: 25639543).

Other names

Src kinasesNon-receptor tyrosine kinasesSFKHematopoietic Src-family kinasesHckFgrLyn

Competitive inhibition of the ATP-binding site within the kinase domain, thereby blocking the phosphorylation of tyrosine residues on downstream signaling substrates.