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Molecular and Cellular Biology, November 2000, p. 8480-8488, Vol. 20, No. 22
Department of Physiological Chemistry and
Centre for Biomedical Genetics, University Medical Center Utrecht,
3584 CG Utrecht,1 and Department of
Molecular Carcinogenesis, Leiden University Medical Center, 2300 RA
Leiden,2 The Netherlands
Received 27 June 2000/Returned for modification 31 July
2000/Accepted 7 August 2000
The transcription factor c-Jun is critically involved in the
regulation of proliferation and differentiation as well as cellular transformation induced by oncogenic Ras. The signal transduction pathways that couple Ras activation to c-Jun phosphorylation are still
partially elusive. Here we show that an activated version of the Ras
effector Rlf, a guanine nucleotide exchange factor (GEF) of the small
GTPase Ral, can induce the phosphorylation of serines 63 and 73 of
c-Jun. In addition, we show that growth factor-induced, Ras-mediated
phosphorylation of c-Jun is abolished by inhibitory mutants of the
RalGEF-Ral pathway. These results suggest that the RalGEF-Ral pathway
plays a major role in Ras-dependent c-Jun phosphorylation.
Ral-dependent regulation of c-Jun phosphorylation includes JNK, a still
elusive JNKK, and possibly Src.
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Ras-Dependent Regulation of c-Jun Phosphorylation Is Mediated
by the Ral Guanine Nucleotide Exchange Factor-Ral
Pathway

*
Corresponding author. Mailing address: Department of
Physiological Chemistry and Centre for Biomedical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The
Netherlands. Phone: 31-30-2538977. Fax: 31-30-2539035. E-mail: J.L.Bos{at}med.uu.nl.
Present address: Wellcome/CRC Institute, Cambridge CB2 1QR, United Kingdom.
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