Bruton’s tyrosine kinase (BTK)

BTK is critical to B-cell development, including proliferation, maturation, differentiation, apoptosis, and cell migration.

BTK is a non-receptor, tyrokinase that is a component of the signal transduction pathway that mediates the B-cell response to encountering its antigen.

BTK activation is critical for homing and retention of healthy B cells and also CLL cells in lymphoid tissue.

BTK engagement with the B cell receptor on the surface of a CLL cell leads to signaling changes in gene expression that drive proliferation and survival.

BTK plays a role in the progression of B-cell lymphoproliferative disorders, such as mantle cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma.

BTK protein is a Tec family tyrosine kinase activated by spleen tyrosine kinase following B-cell-receptor stimulation and which is required for downstream events including calcium release, activation of the NFkB and NFAT pathways, cell survival and proliferation.

BTK family transmit signals through a variety of receptors in B cells and myeloid cells.

BTK expression on myeloid cells, particularly macrophages, changes chemokine and vascular endothelial growth  factor expression, and promotes tumor angiogenesis, invasion and metastasis.

In X-linked agammaglobulinenemia there is a functional mutations in BTK resulting in the virtual absence of all B cells and immunoglobulins leading to recurrent bacterial infections.