The Src Family of Protein Tyrosine Kinases
The protein tyrosine kinases (PTKs) of the Src family play a central role in regulating cellular development, proliferation, and function in a variety of tissues (reviewed in Mustelin 1994a). Their activity is tightly regulated and constitutive activity of these PTKs results in uncontrolled proliferation and even transformation. It has therefore been a major objective to understand how these enzymes are regulated. For many reasons, T lymphocytes have provided a very useful model system to address the mechanisms of Src-related PTK regulation (reviewed in Couture and Mustelin 1995; Mustelin and Burn 1993; Mustelin 1994b) both during development and antigen receptor-mediated activation. The function of a T lymphocyte is induced when it encounters its specific antigen bound to a major histocompatibility (MHC) molecule on the surface of an antigen-presenting cell. This ligand is specifically recognized by the lymphocyte’s multicomponent T-cell antigen receptor (TCR), which contains both polymorphic subunits that are used for antigen/MHC binding, and nonpolymorphic subunits that are used to generate a cascade of events which signal the occupancy of the receptor and lead to modulation of gene expression and of the activity of gene products that are crucial to cell function. If appropriate secondary signals are present, these changes also result in progression through the cell cycle and clonal expansion (Altman et al. 1990; Zenner et al. 1995). A few years ago, the importance of tyrosine phosphorylation in these events was recognized (Mustelin et al. 1990; Mustelin and Altman 1991), and much work has been devoted to the identification of the PTKs involved in T-cell activation, including a few members of the Src family, and the mechanisms by which these enzymes are regulated. In this chapter, we will first describe all nine members of the Src family of PTKs and discuss the molecular mechanisms by which Src family members expressed in T cells are regulated and participate in TCR-mediated T-cell activation.
KeywordsTyrosine Residue Autophosphorylation Site PTPase Activity Conserve Tyrosine Residue Basal Tyrosine Phosphorylation
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