The Tec family of cytoplasmic tyrosine kinases: mammalian Btk, Bmx, Itk, Tec, Txk and homologs in other species

Abstract

Cytoplasmic protein-tyrosine kinases (PTKs) are enzymes involved in transducing a vast number of signals in metazoans. The importance of the Tec family of kinases was immediately recognized when, in 1993, mutations in the gene encoding Bruton's tyrosine kinase (Btk) were reported to cause the human disease X-linked agammaglobulinemia (XLA). Since then, additional kinases belonging to this family have been isolated, and the availability of full genome sequences allows identification of all members in selected species enabling phylogenetic considerations. Tec kinases are endowed with Pleckstrin homology (PH) and Tec homology (TH) domains and are involved in diverse biological processes related to the control of survival and differentiation fate. Membrane translocation resulting in the activation of Tec kinases with subsequent Ca2+ release seems to be a general feature. However, nuclear translocation may also be of importance. The purpose of this essay is to characterize members of the Tec family and discuss their involvement in signaling. The three-dimensional structure, expression pattern and evolutionary aspects will also be considered.

Tec Kinase Itk Forms Membrane Clusters Specifically in the Vicinity of Recruiting Receptors

“…Section 1734 solely to indicate this fact. 1 GFP fragment for YFP1-Itk or YFP2-Itk in the FUGW vector, respectively. The pGFP-Itk was generated by inserting GFP fragment to the N terminus of HA-Itk (24).…”

“…The Tec family of non-receptor tyrosine kinases is the second largest family of non-receptor tyrosine kinases (1). This family, which includes Itk, 2 is involved in transducing signals from a number of receptors, including the T cell receptor, B cell receptor, Fc⑀R, c-Kit, CD28, CD2, CD32, and the erythropoietin receptor (1)(2)(3)(4)(5)(6).…”

“…This family, which includes Itk, 2 is involved in transducing signals from a number of receptors, including the T cell receptor, B cell receptor, Fc⑀R, c-Kit, CD28, CD2, CD32, and the erythropoietin receptor (1)(2)(3)(4)(5)(6). These kinases play important roles in regulating cytokine and immune receptor signals that regulate the immune response (7,8).…”

“…A common feature of these kinases is that they require the activation of PI3 kinase, as well as Src kinase activation for their activity (14 -17). These kinases, including Itk, have a PH domain that allows them to be recruited to the plasma membrane by an activated PI3 kinase (1). Thus, membrane recruitment is a critical component of their activation, and Itk can be found at the plasma membrane of cells, although other events are required for its full activity (17)(18)(19).…”

NK T Cell Precursors Exhibit Differential Cytokine Regulation and Require Itk for Efficient Maturation

“…The fact that a more complete block in NK T cell development does not occur may be due to compensation by other family members. Itk is a member of a larger gene family, that includes Rlk and Tec, both of which are expressed in T and NK cells (47). It has been shown that mice doubly deficient in itk and rlk show increased deficiencies in conventional T cell development compared with the single mutations (48).…”