TY - JOUR T1 - CD45 Can Regulate JAK Activity JF - Science's STKE JO - Sci. STKE SP - tw6 LP - tw6 DO - 10.1126/stke.2001.66.tw6 VL - 2001 IS - 66 A2 - , Y1 - 2001/01/23 UR - http://stke.sciencemag.org/content/2001/66/tw6.abstract N2 - 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] ER -