Tec Kinase Signaling
Tec kinases are non-receptor tyrosine kinases found primarily, but not exclusively, in hematopoietic cells, where they are differentially expressed. Member of the Tec kinase family include Tec, which is found in T-cells , B-cells and liver cells; Bruton's tyrosine kinase (Btk) and IL2-inducible T-cell kinase (Itk/Emt/Tsk), which are essential for antigen-induced B-cell receptor signaling and T-cell activation, respectively; bone marrow tyrosine kinase gene in chromosome X protein (Bmx/Etk), which is also found in epithelial and endothelial cells; Drosophila Esrc29 and Rlk/Txk/Txl. Btk, Itk and Rlk have been studied most extensively as downstream mediators of antigen-activation in T and B cells.
Members of the Tec kinase family can locate to the plasma membrane and to non-plasma membrane micro-environments. Tec kinases are recruited to the plasma membrane or specific micro-environments by a variety of lipid molecules or protein motifs including InsPtd(3,4,5)P3, FERM (a FAK domain), caveolin-1, heterotrimeric G-protein subunits, PKC or F-actin. InsPtd(3,4,5)P3 produced by class I or II PI3-kinases is the dominant plasma membrane (PM) Tec kinase recruiting phospholipid. Bound Tec kinases are activated by many cell surface receptor-associated signalosomes, including specific receptor tyrosine kinases (RTK), cytokine receptor-associated kinases (JAK), integrin associated kinases (FAK), G-protein coupled receptors (GPCR) and antigen T- and B-cell receptor associated kinases, Src and Syk family members (SFK)).
Tec kinases have been studied most extensively in lymphocytes and mast cells. They are often associated with calcium (Ca2+) mobilization and activation of phospholipase-C gamma (PLC-gamma), an upstream regulator of protein kinase-C (PKC) activation through diacylglycerol (DAG) formation and endoplasmic reticulum (ER) calcium mobilization. Tec kinases are involved in a variety of cell processes that include gene expression, calcium mobilization, actin reorganization/adhesion/migration (motility) and survival/apoptosis.
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References:
- August, A. et. al. (1997) Src-induced activation of inducible T cell kinase (ITK) requires phosphatidylinositol 3-kinase activity and the Pleckstrin homology domain of inducible T cell kinase. Proc. Natl. Acad. Sci. USA 94, 11227 -11232.
- Bunnell, S. et. al. (2000) Biochemical interactions integrating Itk with the T cell receptor-initiated signaling cascade. J. Biol. Chem. 276, 2219 -2230.
- Finkelstein, L.D. et. al. (2005) Tec kinases regulate TCR-mediated recruitment of signaling molecules and integrin-dependent cell adhesion. J. Immunol. 175, 5923-5930.
- Fluckiger, A. C. et. al. (1998) Btk/Tec kinases regulate sustained increases in intracellular Ca2+ following B-cell receptor activation. EMBO J. 17, 1973-1985.
- Takesono, A. et. al. (2002) Beyond calcium: new signaling pathways for Tec family kinases. J. Cell Sci. 115, 3039-348.
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Content for this page is provided by Dennis R. Conrad, Ph.D., a Life Science industry consultant with over 25 years of experience in the formulation and optimization of cell culture media. Dr. Conrad's email address is biomediaexpert@earthlink.net
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