Signalling of Bruton's tyrosine kinase, Btk

Bruton's tyrosine kinase, which is encoded by the BTK gene, is a cytoplasmi c protein tyrosine kinase (PTK) crucial for B-cell development and differen tiation. It belongs to the Tec family of PTKs containing several domains th at are characteristic of signalling molecules. In humans, mutations that di srupt the function of this gene lead to the classical XLA syndrome (X-linke d agammaglobulinaemia), a primary immunodeficiency mainly characterized by lack of mature B cells as well as low levels of immunoglobulins. In contras t, animal models of this disease such as the xid mice display profoundly mi lder XLA phenotype. BTK phosphorylation and activation in response to engag ement of the B-cell receptor (BCR) by antigen is a dynamic process whereby a variety of proteins interact with each other and recruit signalling molec ules resulting in a physiological response such as B-cell proliferation and antibody production. The main players, however, that participate in the in tracellular downstream cascade have not yet been identified and are therefo re under intense scrutiny in several laboratories. This review discusses ce rtain aspects of BTK activation following receptor stimulation by agonists and how this event is translated into the biochemical signals within the ce ll that eventually lead to nuclear responses.