BTK (Bruton Tyrosine Kinase), also known as B-Cell Progenitor Kinase, EC 2.7.10.2, AGMX1, ATK, BPK, is a non-receptor tyrosine kinase indispensable for B lymphocyte development, differentiation and signaling. It acts as a platform to bring together a diverse array of signaling proteins and is implicated in cytokine receptor signaling pathways. Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation. After BCR engagement and activation at the plasma membrane, BTK can phosphorylate PLCG2 at several sites, igniting the downstream signaling pathway through calcium mobilization, followed by activation of the protein kinase C (PKC) family members. It also plays an important role in the function of immune cells of innate as well as adaptive immunity, as a component of the Toll-like receptors (TLR) pathway. BTK can be activated by phosphorylation. In primary B lymphocytes, it is almost always non-phosphorylated and is thus catalytically inactive. Stimulation of TLR8 and TLR9 causes BTK activation. As a negative feedback mechanism to fine-tune BCR signaling, activated PRKCB down-modulates BTK function via direct phosphorylation of BTK at Ser-180, resulting in translocation of BTK back to the cytoplasmic fraction. PIN1, SH3BP5, and IBTK were also identified as BTK activity inhibitors. Interaction with CAV1 leads to dramatic down-regulation of the kinase activity of BTK. LFM-13A is a specific inhibitor of BTK.
