Editors' ChoiceProtein Phosphatases

JSP-1 Activates Jnk Through MKK4

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Science's STKE  27 Nov 2001:
Vol. 2001, Issue 110, pp. tw433
DOI: 10.1126/stke.2001.110.tw433

Shen et al. have identified a new dual-specificity protein phosphatase and characterized its function. Whereas dual-specificity phosphatases usually inactivate mitogen-activated protein kinases (MAPKs), this new protein phosphatase specifically activates the MAPK Jnk, and is termed Jun NH2-terminal kinase (Jnk) stimulatory phosphatase-1 (JSP-1). Cells overexpressing JSP-1 did not inactivate MAPKs. JSP-1 did not activate Jnk directly, but rather activated MKK4, the MAPK kinase known to activate Jnk. Increased phosphorylation of overexpressed MKK4 was observed in cells also expressing wild-type JSP-1 but not in cells expressing catalytically inactive JSP-1. The authors propose that JSP-1 might remove phosphates from MKK4 that prevent the activation of that kinase. Overexpression of dominant-negative MKK4 inhibited the ability of JSP-1 to activate Jnk, indicating that JSP-1-dependent activation of Jnk requires MKK4. The identification of JSP-1 introduces a new level of regulation to Jnk activation.

Y. Shen, R. Luche, B. Wei, M. L. Gordon, C. D. Diltz, N. K. Tonks, Activation of the Jnk signaling pathway by a dual-specificity phosphatase, JSP-1. Proc. Natl. Acad. Sci U.S.A. 98, 13613-13618 (2001). [Abstract] [Full Text]