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CD45: new jobs for an old acquaintance

Nature Immunology volume 2, pages 389–396 (2001)Cite this article

Abstract

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.

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Figure 1: Structure of CD45.
Figure 2: Control of p56lck activation by CD45.
Figure 3: Control of cytokine receptor signaling by CD45.

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Acknowledgements

We apologize that we could not cite many excellent studies on CD45. Supported by grants from the Canadian Institute for Health Research (CIHR), the National Cancer Institute (NCI) of Canada, CANVAC and Amgen Inc.

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  1. Junko Irie-Sasaki & Takehiko Sasaki

    Present address: Department of Pharmacology, Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8613, Japan

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  1. Departments of Medical Biophysics and Immunology, Amgen Research Institute and Ontario Cancer Institute, Princess Margaret Hospital, University Health Network, University of Toronto, 620 University Avenue, Toronto, M5G 2C1, ON, Canada

    Josef M. Penninger, Junko Irie-Sasaki, Takehiko Sasaki & Antonio J. Oliveira-dos-Santos

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Penninger, J., Irie-Sasaki, J., Sasaki, T. et al. CD45: new jobs for an old acquaintance. Nat Immunol 2, 389–396 (2001). https://doi.org/10.1038/87687

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