Editors' ChoiceImmunology

CD45 Regulation by Alternative Splicing

Science's STKE  13 Aug 2002:
Vol. 2002, Issue 145, pp. tw296-TW296
DOI: 10.1126/stke.2002.145.tw296

CD45 is a receptor-type protein tyrosine phosphatase that positively regulates T cell antigen receptor signaling. It is thought that dimerization inhibits CD45 activity, although a regulatory ligand for CD45 has remained elusive. Xu and Weiss offer one possible explanation for this. Dimerization may be determined by the CD45 isoform present at the cell surface. Alternative splicing of three consecutive exons generates isoforms that vary in their degree of glycosylation. Isoform expression is highly regulated and switches from the most highly glycosylated to the least glycosylated isoform during T cell activation. The authors show that the least glycosylated isoform dimerizes most efficiently in primary and transfected T cells. Expression of the least glysocylated isoform correlated with decreased TCR signaling. The authors propose that TCR signaling may induce the expression of splicing factors that cause a switch in isoform expression. This could serve as part of a negative feedback loop to terminate an immune response.

Z. Xu, A. Weiss, Negative regulation of CD45 by differential homodimerization of the alternatively spliced isoforms. Nat. Immunology 3, 764-771 (2002). [Online Journal]

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