AJP - Cell Physiology, Vol 263, Issue 6 C1119-C1140, Copyright © 1992 by American Physiological Society
Signal transduction by T-cell receptors: mobilization of Ca and regulation of Ca-dependent effector molecules
B. A. Premack and P. Gardner
Department of Medicine, Falk Cardiovascular Research Center, Stanford University, California 94305-5246.
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.
