IMMUNOLOGY: Deactivation by Degrees

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Science  16 Aug 2002:
Vol. 297, Issue 5584, pp. 1095a
DOI: 10.1126/science.297.5584.1095a

The cell-surface tyrosine phosphatase, CD45, provides critical regulation of lymphocyte activation. By dephosphorylating inhibitory tyrosine residues on protein tyrosine kinases (PTKs), CD45 facilitates signaling through the T cell receptor. This phosphatase activity is constitutive in the CD45 monomer but is down-regulated through dimerization.

CD45 is expressed as distinct isoforms, generated through alternative exon splicing of the extracellular portion of the molecule. Xu and Weiss now show that these isoforms are the key to how dimer formation is regulated. The smallest isoform (CD45RO) dimerizes more readily than its longer counterparts, correlating with reduced levels of T cell activation and reduced levels of posttranslational modification by O-linked glycosylation and sialylation. Thus, longer isoforms, which are more prevalent on resting T cells, appear to be preferentially maintained as active monomers because increased sugars would impede dimer formation. Production of smaller isoforms after T cell activation would thus promote dimerization, reducing CD45 phosphatase activity and dampening down T cell responses. — SJS

Nature Immunol. 3, 764 (2002).

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