Bruton tyrosine kinase (BTK) belongs to the TEC family of nonreceptor kinases and is expressed in various hematopoietic cells, including B cells, myeloid cells, and platelets (1). Within B cells, BTK plays a critical role in the B cell receptor (BCR) signaling pathway, where it contributes to the differentiation, proliferation, and survival of normal B cells (2).

BCR pathway activation begins when antigen stimulation induces phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAM) by SRC family protein tyrosine kinases (e.g., LYN; ref. 2). Consequently, spleen tyrosine kinase (SYK) becomes activated, facilitating recruitment of BTK to the cell membrane and subsequent phosphorylation of tyrosine 551 (Y551) within BTK's kinase domain (2). This activation of BTK prompts autophosphorylation at a second site, tyrosine 223 (Y223), located within BTK's SH3 domain (3). With complete activation achieved, BTK can then phosphorylate its immediate downstream target, phospholipase-Cγ2...

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