The Btk subfamily of cytoplasmic tyrosine kinases: structure, regulation and function

Abstract

The genetic defect associated with two closely related primary immunodeficiencies was recently identified as a deficiency of function of a new cytoplasmic tyrosine kinase, Bruton's tyrosine kinase (Btk). Btk and related genes expressed primarily in hematopoietic cells (Itk, Tec, Drsrc28C and Txk) comprise a new subfamily of cytoplasmic tyrosine kinases. These proteins share significant structural and sequence homology including an amino-terminal pleckstrin homology (PH) domain not present in other cytoplasmic tyrosine kinase subfamilies. This domain plays an essential role in regulation and function of the Btk subfamily proteins. Genetic evidence supports a critical role for Btk in B-lineage development. Additional studies demonstrate activation of these proteins in multiple hematopoietic signaling pathways including the B cell antigen receptor, several cytokine receptors, and a potential novel role in heterotrimeric G protein associated receptor signaling.