HCK Antibodies

Structure of HCK

HCK is a tyrosine kinase in the Src family that is mainly expressed in myeloid cells and has a typical modular structure: the N-terminal myristic acylation site mediates membrane localization, the SH3 and SH2 domains recognize proline-rich sequences and phosphorylated tyrosine, respectively, and the C-terminal kinase domain contains an ATP-binding pocket and a catalytic center. Its uniqueness lies in maintaining a self-inhibitory state through intramolecular interactions - SH3 binds to the junction region and SH2 binds to the C-terminal pTyr522. This ingenious conformational regulation enables it to respond rapidly to external stimuli. When activated, the SH3/SH2 domain instead binds to effector proteins, while Tyr411 autophosphylation enhances activity, thereby precisely regulating the activation, migration and phagocytosis functions of myeloid cells. This special structural feature of HCK makes it an important target for the treatment of inflammatory diseases.

Fig. 1 Structure of Hck.¹

Functions of HCK

HCK is a core regulatory factor for signal transduction in myeloid cells and plays multiple functions in immune responses and inflammatory reactions.

The activity of HCK exhibits typical biphase regulatory characteristics: it maintains self-inhibition through phosphorylation of C-terminal Tyr522 in the basal state, but can be rapidly activated and form a positive feedback amplification signal after stimulation. This precise spatiotemporal regulation makes it a key molecular node connecting innate immunity and adaptive immunity. Unlike the broad-spectrum action of most kinases, HCK exhibits obvious myeloid cell specificity, which provides it with a unique advantage as a therapeutic target.

Applications of HCK and HCK Antibody in Literature

1. Chen, Man, et al. "HCK induces macrophage activation to promote renal inflammation and fibrosis via suppression of autophagy." Nature communications 14.1 (2023): 4297. https://doi.org/10.1038/s41467-023-40086-3

Research has found that hematopoietic cell kinase (HCK) exacerbates renal inflammation and fibrosis in chronic kidney disease (CKD) by promoting M1-type polarization, proliferation and migration of macrophages. HCK antibodies or inhibitors alleviate fibrosis by inhibiting autophagic flow in macrophages. Targeting HCK may become a new strategy for anti-renal fibrosis.

2. Scholz, Glen, Kellie Cartledge, and Ashley R. Dunn. "Hck enhances the adherence of lipopolysaccharide-stimulated macrophages via Cbl and phosphatidylinositol 3-kinase." Journal of Biological Chemistry 275.19 (2000): 14615-14623. https://doi.org/10.1074/jbc.275.19.14615

Research has found that HCK antibodies can inhibit the adhesion of LPS-activated macrophages. HCK directly phosphorylates Cbl through the SH3 domain, promoting its binding to the PI3K p85 subunit, thereby enhancing the cytoskeletal recombination and adhesion ability of macrophages. This process depends on the activity of Src family kinases.

3. Kong, Xiangxi, et al. "Hematopoietic cell kinase (HCK) is essential for NLRP3 inflammasome activation and lipopolysaccharide-induced inflammatory response in vivo." Frontiers in pharmacology 11 (2020): 581011. https://doi.org/10.3389/fphar.2020.581011

Research has found that HCK antibodies reduce the release of IL-1β and caspase-1(P20) by inhibiting the activation of the NLRP3 inflammasome. HCK directly binds to the NBD and LRR domains of NLRP3. Its inhibitors can block ASC oligomerization and alleviate LPS-induced liver inflammation, suggesting that targeting HCK may be effective in treating acute inflammatory diseases.

4. Welch, Heidi, and Isabelle Maridonneau-Parini. "Hck is activated by opsonized zymosan and A23187 in distinct subcellular fractions of human granulocytes." Journal of Biological Chemistry 272.1 (1997): 102-109. https://doi.org/10.1074/jbc.272.1.102

Studies have shown that HCK antibodies can regulate the activation of neutrophils. HCK is selectively activated by different stimuli (conditioning yeoglycan /A23187) in the particle-rich region and membrane region, participating in the regulation of degranulation reactions, suggesting that it has specific functions in different subcellular compartments.

5. Yokoyama, Noriko, and W. Todd Miller. "Biochemical properties of the Cdc42-associated tyrosine kinase ACK1: Substrate specificity, autophosphorylation, and interaction with Hck." Journal of Biological Chemistry 278.48 (2003): 47713-47723. https://doi.org/10.1074/jbc.M306716200

Research has found that HCK binds to the C-terminal proline-rich region of ACK1 through the SH3 domain and phosphorylates ACK1 (Tyr284 site), thereby enhancing its kinase activity. This interaction reveals the key role of HCK in regulating the ACK1 signaling pathway.

Creative Biolabs: HCK Antibodies for Research

Creative Biolabs specializes in the production of high-quality HCK antibodies for research and industrial applications. Our portfolio includes monoclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

• Custom HCK Antibody Development: Tailor-made solutions to meet specific research requirements.
• Bulk Production: Large-scale antibody manufacturing for industry partners.
• Technical Support: Expert consultation for protocol optimization and troubleshooting.
• Aliquoting Services: Conveniently sized aliquots for long-term storage and consistent experimental outcomes.

For more details on our HCK antibodies, custom preparations, or technical support, contact us at please contact us.