Tyrosine-protein kinase Fgr (FGR)

Tyrosine-protein kinase Fgr is a non-receptor tyrosine kinase and a member of the Src family (SFK), primarily expressed in hematopoietic cells such as neutrophils, monocytes, and macrophages. It serves as a critical mediator of innate immune signaling, acting downstream of cell surface receptors like integrins and Fc receptors to regulate processes such as phagocytosis, cell adhesion, and the release of inflammatory cytokines. In healthy tissues, Fgr helps coordinate the cellular response to extracellular stimuli and maintains the integrity of the actin cytoskeleton. However, its dysregulation is strongly linked to the progression of various malignancies, including acute myeloid leukemia (AML) and several solid tumors, where it promotes cell proliferation and survival. Fgr is a target for several clinically approved multi-kinase inhibitors, such as dasatinib and bosutinib, which are utilized in the treatment of leukemias. Despite its therapeutic potential, the use of inhibitors targeting Fgr often involves managing systemic side effects and off-target toxicities due to the high structural homology among Src family members.

Other names

Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homologProto-oncogene c-Fgrp55-Fgrp58-Fgrp58c-FgrSRC2FGR proto-oncogene, Src family tyrosine kinase

Competitive inhibition of the ATP-binding site within the tyrosine kinase domain, preventing autophosphorylation and downstream signaling through pathways such as MAPK/ERK and PI3K/Akt.