Sci. STKE, 23 January 2001
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).
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