Ras-dependent regulation of c-Jun phosphorylation is mediated by the Ra1 guanine nucleotide exchange factor-Ra1 pathway

被引:64
作者
De Ruiter, ND
Wolthuis, RMF
van Dam, H
Burgering, BMT
Bos, JL
机构
[1] Univ Utrecht, Med Ctr, Dept Physiol Chem, NL-3584 CG Utrecht, Netherlands
[2] Univ Utrecht, Med Ctr, Ctr Biomed Genet, NL-3584 CG Utrecht, Netherlands
[3] Leiden Univ, Med Ctr, Dept Mol Carcinogenesis, NL-2300 RA Leiden, Netherlands
关键词
D O I
10.1128/MCB.20.22.8480-8488.2000
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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, sere 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.
引用
收藏
页码:8480 / 8488
页数:9
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