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Molecular and Cellular Biology, April 2005, p. 2733-2743, Vol. 25, No. 7
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.7.2733-2743.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Role of the JIP4 Scaffold Protein in the Regulation of Mitogen-Activated Protein Kinase Signaling Pathways{dagger}

Nyaya Kelkar,{ddagger} Claire L. Standen, and Roger J. Davis*

Howard Hughes Medical Institute and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts

Received 13 November 2004/ Returned for modification 16 December 2004/ Accepted 22 December 2004

The c-Jun NH2-terminal kinase (JNK)-interacting protein (JIP) group of scaffold proteins (JIP1, JIP2, and JIP3) can interact with components of the JNK signaling pathway and potently activate JNK. Here we describe the identification of a fourth member of the JIP family. The primary sequence of JIP4 is most closely related to that of JIP3. Like other members of the JIP family of scaffold proteins, JIP4 binds JNK and also the light chain of the microtubule motor protein kinesin-1. However, the function of JIP4 appears to be markedly different from other JIP proteins. Specifically, JIP4 does not activate JNK signaling. In contrast, JIP4 serves as an activator of the p38 mitogen-activated protein (MAP) kinase pathway by a mechanism that requires the MAP kinase kinases MKK3 and MKK6. The JIP4 scaffold protein therefore appears to be a new component of the p38 MAP kinase signaling pathway.

* Corresponding author. Mailing address: Howard Hughes Medical Institute, Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation St., Worcester, MA 01605. Phone: (508) 856-6054. Fax: (508) 856-3210. E-mail: Roger.Davis{at}Umassmed.Edu.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} Present address: Enzo Biochem, Farmingdale, NY 11735.

Molecular and Cellular Biology, April 2005, p. 2733-2743, Vol. 25, No. 7
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.7.2733-2743.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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