Signaling network of the Btk family kinases

The Btk family kinases represent new members of nonreceptor tyrosine kinase s,which include Btk/Atk, Itk/Emt/Tsk, Bmx/Etk, and Tee. They are characteri zed by having four structural modules: PH (pleckstrin homology) domain, SH3 (Src homology 3) domain, SH2 (Src homology 2) domain and kinase (Src homol ogy 1) domain. Increasing evidence suggests that, like Src-family kinases, Btk family kinases play central but diverse modulatory roles in various cel lular processes, They participate in signal transduction in response to vir tually all types of extracellular stimuli which are transmitted by growth f actor receptors, cytokine receptors, G-protein coupled receptors, antigen-r eceptors and integrins, They are regulated by many non-receptor tyrosine ki nases such as Src, Jak, Syk and FAK family kinases, In turn, they regulate many of major signaling pathways including those of PI3K, PLC gamma and PKC , Both genetic and biochemical approaches have been used to dissect the sig naling pathways and elucidate their roles in growth, differentiation and ap optosis, An emerging new role of this family of kinases is cytoskeletal reo rganization and cell motility, The physiological importance of these kinase s was amply demonstrated hy their link to the development of immunodeficien cy diseases, due to germ-line mutations. The present article attempts to re view the structure and functions of Btk family kinases by summarizing our c urrent knowledge on the interacting partners associated with the different modules of the kinases and the diverse signaling pathways in which they are involved.