CD45: new jobs for an old acquaintance.
Identified as the first and prototypic transmembrane protein tyrosine phosphatase (PTPase), CD45 has been extensively studied for over two decades and is thought to be important for positively regulating antigen-receptor signaling via the dephosphorylation of Src kinases. However, new evidence indicates that CD45 can function as a Janus kinase PTPase that negatively controls cytokine-receptor signaling. A point mutation in CD45, which appears to affect CD45 dimerization, and a genetic polymorphism that affects alternative CD45 splicing are implicated in autoimmunity in mice and multiple sclerosis in humans. CD45 is expressed in multiple isoforms and the modulation of specific CD45 splice variants with antibodies can prevent transplant rejections. 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 differentiation of multiple hematopoietic cell lineages, autoimmunity and antiviral immunity.
Penninger
J M
JM
Amgen Research Institute and Ontario Cancer Institute, Princess Margaret Hospital, University Health Network, Department of Medical Biophysics, University of Toronto, 620 University Avenue, Toronto, ON M5G 2C1, Canada. Jpenning@amgen.com
Irie-Sasaki
J
J
Sasaki
T
T
Oliveira-dos-Santos
A J
AJ
D015551:Autoimmunity; D002454:Cell Differentiation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D009369:Neoplasms / Q000209:etiology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D018121:Receptors, Cytokine / Q000378:metabolism*; D015398:Signal Transduction; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D018121:Receptors, Cytokine; D011505:Protein-Tyrosine Kinases; D019061:src-Family Kinases; D017493:Leukocyte Common Antigens