Signal transduction by T-cell receptors: mobilization of Ca and regulation of Ca-dependent effector molecules.
There have been major advances over the last several years in understanding the molecular basis of signaling by the T lymphocyte (T-cell) antigen receptor. In this article we discuss the early phases of T-cell activation with an emphasis on receptor-associated signaling molecules, mobilization of Ca, and on the possible roles of Ca in signal transduction. Ligation of the extracellular domains of the T-cell receptor activates receptor-associated tyrosine kinases that can phosphorylate the gamma-isoform of phospholipase C, increasing its catalytic activity. This leads to production of inositol 1,4,5-trisphosphate, release of stored intracellular Ca, and activation of Ca-permeable plasma membrane channels. Many of the critical T-cell signal transducing enzymes such as phospholipase C and protein kinase C contain intrinsic Ca-binding domains, but for the most part the rise in cytoplasmic Ca is transduced by specialized Ca-binding proteins that lack catalytic domains. The Ca-binding proteins found in T-cells include members of both the EF-hand and annexin families, as well as other types of Ca-binding proteins. In T-cells, a number of important kinases, phosphatases, and cytoskeleton-modulating enzymes are functionally Ca dependent but have no Ca-binding domains and therefore must sense changes in the cytoplasmic Ca level through interactions with Ca-binding proteins.
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism / Q000502:physiology; D003593:Cytoplasm / Q000378:metabolism; D004594:Electrophysiology; D004798:Enzymes / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015398:Signal Transduction
D002135:Calcium-Binding Proteins; D004798:Enzymes; D007473:Ion Channels; D011948:Receptors, Antigen, T-Cell; D002118:Calcium