Btk

Bruton tyrosine kinase (Btk) is a member of the Tec family kinases with a well-characterized role in B-cell antigen receptor (BCR)-signaling and B-cell activation.

Btk plays a crucial role in B cell development and activation through the BCR signaling pathway and represents a new target for diseases characterized by inappropriate B cell activity. Btk is a kinase expressed exclusively in B cells and myeloid cells and has a well characterized, vital role in B cells highlighted by the human primary immune deficiency disease, X-linked agammaglobulinemia (XLA), which results from mutation in the Btk gene. Btk plays an essential role in the BCR signaling pathway. Antigen binding to the BCR results in B cell receptor oligomerization, Syk and Lyn kinase activation, followed by Btk kinase activation. Once activated, Btk forms a signaling complex with proteins such as BLNK, Lyn, and Syk and phosphorylates phospholipase C (PLC)γ2. This leads to downstream release of intracellular Ca²⁺ stores and propagation of the BCR signaling pathway through extracellular signal-regulated kinase and NF-κB signaling, ultimately resulting in transcriptional changes to foster B cell survival, proliferation, and/or differentiation.