CD45: new jobs for an old acquaintance

Identified as the first and prototypic transmembrane protein tyrosine phosp hatase (PTPase), CD45 has been extensively studied for over two decades and is thought to be important for positively regulating antigen-receptor sign aling via the dephosphorylation of Src kinases, However, new evidence indic ates that CD45 can function as a Janus kinase PTPase that negatively contro ls cytokine-receptor signaling. A point mutation in CD45, which appears to affect CD45 dimerization, and a genetic polymorphism that affects alternati ve CD45 splicing are implicated in autoimmunity in mice and multiple sclero sis in humans. CD45 is expressed in multiple isoforms and the modulation of specific CD45 splice variants with antibodies can prevent transplant rejec tions. In addition, loss of CD45 can affect microglia activation in a mouse model for Alzheimer's disease. Thus, CD45 is moving rapidly back into the spotlight as a drug target and central regulator involved in differentiatio n of multiple hematopoietic cell lineages, autoimmunity and antiviral immun ity.