Journal article
Receptor for RACK1 Mediates Activation of JNK by Protein Kinase C
Molecular cell, Vol.19(3), pp.309-320
2005
DOI: 10.1016/j.molcel.2005.06.025
PMCID: PMC2953422
PMID: 16061178
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, TNFα, 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.
Details
- Title: Subtitle
- Receptor for RACK1 Mediates Activation of JNK by Protein Kinase C
- Creators
- Pablo López-Bergami - Department of Oncological Sciences, Mount Sinai School of Medicine, New York, New York 10029Hasem Habelhah - Department of Oncological Sciences, Mount Sinai School of Medicine, New York, New York 10029Anindita Bhoumik - Signal Transduction Program, The Burnham Institute, La Jolla, California 92037Weizhou Zhang - Department of Microbiology, Mount Sinai School of Medicine, New York, New York 10029Lu-Hai Wang - Department of Microbiology, Mount Sinai School of Medicine, New York, New York 10029Ze’ev Ronai - Signal Transduction Program, The Burnham Institute, La Jolla, California 92037
- Resource Type
- Journal article
- Publication Details
- Molecular cell, Vol.19(3), pp.309-320
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.molcel.2005.06.025
- PMID
- 16061178
- PMCID
- PMC2953422
- ISSN
- 1097-2765
- eISSN
- 1097-4164
- Language
- English
- Date published
- 2005
- Academic Unit
- Pathology; Radiation Oncology
- Record Identifier
- 9984047788402771
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