Identification of ROCK1 as an upstream activator of the JIP-3 to JNK signaling axis in response to UVB damage

Pat P. Ongusaha, Hank H. Qi, Lakshmi Raj, Young Bum Kim, Stuart A. Aaronson, Roger J. Davis, Yang Shi, James K. Liao, Sam W. Lee

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Although apoptosis triggered by ultraviolet B (UVB)-mediated activation of the c-Jun N-terminal kinase (JNK) pathway is mediated by both intrinsic and extrinsic pathways, the mechanism of initiation of JNK activation remains obscure. Here, we report the characterization of the JNK-interacting protein 3 (JIP-3) scaffolding protein as an interacting partner of Rho-associated kinase 1 (ROCK1), as determined by tandem affinity protein purification. Upon UVB-induced stress in keratinocytes, ROCK1 was activated, bound to JIP-3, and activated the JNK pathway. Moreover, phosphorylation of JIP-3 by ROCK1 was crucial for the recruitment of JNK. Inhibition of the activity of ROCK1 in keratinocytes resulted in decreased activation of the JNK pathway and thus a reduction in apoptosis. ROCK1+/- mice exhibited decreased UVB-mediated activation of JNK and apoptosis relative to wild-type mice. Our findings present a new molecular mechanism by which ROCK1 functions as a UVB sensor that regulates apoptosis, an important event in the prevention of skin cancer.

Original languageEnglish
Pages (from-to)ra14
JournalScience Signaling
Volume1
Issue number47
DOIs
StatePublished - 25 Nov 2008

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