Bruton tyrosine kinase (BTK) (BTK)

Bruton tyrosine kinase (BTK) is a non-receptor tyrosine kinase of the Tec family that is essential for B-cell development and signaling (UniProt P35991). It acts as a key signaling node downstream of the B-cell receptor (BCR), where its activation leads to the recruitment of various adapter proteins and the activation of pathways such as NF-kappaB and MAPK, which promote B-cell survival and proliferation (PubMed: 24507509). In B-cell malignancies like chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), BTK is often overactive, contributing to the growth and trafficking of malignant cells (NIH: StatPearls - NBK470181). Ibrutinib, the first-in-class BTK inhibitor, binds covalently to the Cys481 residue in the ATP-binding domain, effectively shutting down the kinase activity and inducing apoptosis or growth arrest in tumor cells (PubChem CID 24821094). Beyond its role in oncology, BTK is also involved in Fc receptor signaling in mast cells and macrophages, making it a potential target for treating autoimmune and inflammatory conditions (PubMed: 30104678).

Other names

Bruton agammaglobulinemia tyrosine kinaseAGMX1ATKBPKPSCTK1Tyrosine-protein kinase BTK

Inhibition of kinase activity by binding to the ATP-binding pocket, often through covalent modification of the Cys481 residue, which blocks downstream B-cell receptor signaling.