Member of the Tec family of cytoplasmic protein tyrosine kinases, Bruton’s agammaglobulinemia tyrosine kinase (Bruton’s tyrosine kinase, Btk) is expressed in many hematopoietic cell lineages. Tec family kinases (TFKs) form the second largest family of cytoplasmic tyrosine kinases in mammalian cells and include, in addition to Btk, Tec, Itk, Txk (also known as Rlk), and bone marrow tyrosine kinase gene on chromosome X (Bmx).
Btk is involved in various signaling pathways, including the B cell receptor (BCR) pathway in B lymphocytes, and acts as a crucial regulator of cellular differentiation, activation, proliferation and survival.
Btk is activated by the upstream Src-family kinases Blk, Lyn and Fyn, and Btk in turn phosphorylates and activates phospholipase-Cγ(PLCγ), leading to Ca2+ mobilization and activation of NF-κB and MAP kinase pathways.
The aberrant activation of B-cells plays a central role in the pathogenesis of various autoimmune diseases and B-cell lymphomas.
For reviews about Bruton’s tyrosine kinase see:
a). Abdalla JM et al., Bruton’s tyrosine kinase (Btk): function, regulation, and transformation with special emphasis on the PH domain. Immunol. Rev. 228: 58-73, 2009.
b). Lindvall JM et al., Bruton’s tyrosine kinase: cell biology, sequence conservation, mutation spectrum, siRNA modifications, and expression profiling. Immunol. Rev. 203: 200-215, 2005.
B-cell receptor (BCR) ligation activates phosphatidylinositol-3-kinase (PI3K) resulting in the production of the phosphoinositide, phosphatidylinositol-3,4,5-trisphosphate (PIP3). PIP3 generation leads to recruitment of several intracellular signaling proteins including Btk. In addition to the BCR, the activation of Btk can also occur following the stimulation of a diverse array of cell-surface receptors, the common denominator of which is the generation of PIP3.
Btk gets phosphorylated, becomes fully active and executes downstream signaling duties.
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