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Mol Cell. 2005 Aug 5;19(3):309-20.

RACK1 mediates activation of JNK by protein kinase C [corrected].

Author information

1
Department of Oncological Sciences, Mount Sinai School of Medicine, New York, New York 10029, USA.

Erratum in

  • Mol Cell. 2005 Aug 19;19(4):578-9.

Abstract

Activation of the Jun-N-terminal kinase (JNK) signaling cascade by phorbol esters (TPA) or protein kinase C (PKC) is well documented, although the underlying mechanism is not known. Here, we demonstrate that the receptor for activated C kinase 1 (RACK1) serves as an adaptor for PKC-mediated JNK activation. Phosphorylation of JNK by PKC occurs on Ser129 and requires the presence of RACK1. Ser129 phosphorylation augments JNK phosphorylation by MKK4 and/or MKK7 and is required for JNK activation by TPA, TNFalpha, UV irradiation, and PKC, but not by anisomycin or MEKK1. Inhibition of RACK1 expression by siRNA attenuates JNK activation, sensitizes melanoma cells to UV-induced apoptosis, and reduces their tumorigenicity in nude mice. In finding the role of RACK1 in activation of JNK by PKC, our study also highlights the nature of crosstalk between these two signal-transduction pathways.

PMID:
16061178
PMCID:
PMC2953422
DOI:
10.1016/j.molcel.2005.06.025
[Indexed for MEDLINE]
Free PMC Article

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