CD45 and the immune response.
CD45 is a major transmembrane glycoprotein expressed on all nucleated hematopoietic cells. Eight isoforms of CD45 are distributed through the immune system according to cell type and degree of cellular differentiation. Heterogeneity among the isoforms is found entirely in the extracellular domain, arising from the differential splicing of up to four exons of a single gene. The control of isoform expression suggests that the extracellular domain may participate in protein-protein interactions with isoform-specific ligands. The intracellular domain of CD45 is large (approximately 700 amino acids), identical for all isoforms, and highly conserved across species. Two nonidentical intracellular sequences of about 240 amino acids that are homologous with a tyrosine phosphatase consensus sequence have been identified. Studies with purified CD45 have shown that all isoforms possess enzymatic activity in in vitro assays. In several T and B cell lines and in natural killer cells, it appears that CD45 is required for optimal signal transduction after stimulation through a number of surface receptors. Although an in vivo substrate has not been identified conclusively, one model suggests that CD45 functions to dephosphorylate a negative-regulatory tyrosine residue on one or more protein tyrosine kinases involved in receptor-mediated second messenger formation. In T cells, the src family kinases, lck and fyn, are candidates for this regulated kinase. In this review, some of the structural and functional aspects of CD45 and its role in signal transduction in the immune system are discussed.
Donovan
J A
JA
Koretzky
G A
GA
D000818:Animals; D006801:Humans; D017493:Leukocyte Common Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D051379:Mice; D008954:Models, Biological; D015394:Molecular Structure; D012326:RNA Splicing; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology
D008562:Membrane Glycoproteins; D011948:Receptors, Antigen, T-Cell; D017493:Leukocyte Common Antigens