Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Sci. STKE, 23 January 2001
Vol. 2001, Issue 66, p. tw6
[DOI: 10.1126/stke.2001.66.tw6]

EDITORS' CHOICE

Immunology CD45 Can Regulate JAK Activity

CD45, a transmembrane protein tyrosine phosphatase expressed in immune cells, regulates antigen receptor-mediated signal transduction by controlling the phosphorylation state (and activation) of several kinases. Irie-Sasaki et al. now provide evidence that suggests CD45 involvement in cytokine signaling by regulating Janus kinase (JAK) activity. CD45-deficient interleukin 3 (IL-3)-treated bone marrow-derived mast cells (BMMCs) exhibited greater proliferation, which correlated with increased levels of phosphorylated JAK2 and JAK2 kinase activity. Similarly, CD45-deficient BMMCs exhibited greater phosphorylation of STAT (signal transducer and transactivator) proteins. In vitro, CD45 dephosphorylated JAKs, as well as a catalytically inactive CD45 mutant associated with JAK2. Overexpression of CD45 in interferon-α (IFN-α)-treated COS cells led to decreased phosphorylation of JAK1. In vivo, CD45 knockout mice survived infection with Coxsackie B3 virus, which implies that a lack of CD45 function resulted in greater immune response, presumably mediated by greater sustained activation of JAK and STAT activity.

J. Irie-Sasaki, T. Sasaki, W. Matsumoto, A. Opavsky, M. Cheng, G. Welstead, E. Griffiths, C. Krawczyk, C. D. Richardson, K. Aitken, N. Iscove, G. Koretzky, P. Johnson, P. Liu, D. M. Rothstein, J. M. Penninger, CD45 is a JAK phosphatase and negatively regulates cytokine receptor signaling. Nature 409, 349-354 (2001). [Online Journal]

Citation: CD45 Can Regulate JAK Activity. Sci. STKE 2001, tw6 (2001).


To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882