HCK
Description
The HCK (HCK proto-oncogene, Src family tyrosine kinase) is a protein-coding gene located on chromosome 20.
HCK is an enzyme encoded by the HCK gene in humans. It is a tyrosine-protein kinase with five distinct domains: two terminal domains and three SH domains. The N-terminal domain is crucial for lipid modifications, while the C-terminal domain contains a regulatory tyrosine residue. The SH1 domain houses the active site, while the SH2 and SH3 domains are tightly bound in the inactive state. HCK resides in the cytoplasm and remains inactive until stimulated by TLR4 or IL-2. Upon stimulation, C-terminal tyrosine residues are dephosphorylated, disrupting the inactive conformation and activating HCK.
HCK, a non-receptor tyrosine-protein kinase, plays a crucial role in regulating innate immune responses within hematopoietic cells. It acts as a signal transducer from cell surface receptors, influencing a variety of cellular processes including neutrophil, monocyte, macrophage, and mast cell functions. This includes phagocytosis, cell survival and proliferation, cell adhesion, and migration. HCK operates downstream of receptors that bind the Fc region of immunoglobulins such as FCGR1A and FCGR2A, but also CSF3R, PLAUR, the receptors for IFNG, IL2, IL6 and IL8, and integrins like ITGB1 and ITGB2. During phagocytosis, HCK mediates the mobilization of secretory lysosomes, degranulation, and the activation of NADPH oxidase, leading to the respiratory burst. It contributes to the release of inflammatory molecules, promotes actin cytoskeleton reorganization and polymerization, and facilitates the formation of podosomes and cell protrusions. HCK also inhibits TP73-mediated transcription activation and apoptosis. Upon activation of immunoglobulin gamma Fc region receptors, HCK phosphorylates CBL, as well as ADAM15, BCR, ELMO1, FCGR2A, GAB1, GAB2, RAPGEF1, STAT5B, TP73, VAV1 and WAS.
HCK is also known as AIPCV, JTK9, p59Hck, p61Hck.
