Ras依赖性的c-Jun磷酸化调节由Ral鸟嘌呤核苷酸交换因子-Ral途径介导。
Ras-dependent regulation of c-Jun phosphorylation is mediated by the Ral guanine nucleotide exchange factor-Ral pathway.
作者信息
de Ruiter N D, Wolthuis R M, van Dam H, Burgering B M, Bos J L
机构信息
Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands.
出版信息
Mol Cell Biol. 2000 Nov;20(22):8480-8. doi: 10.1128/MCB.20.22.8480-8488.2000.
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.
转录因子c-Jun在增殖、分化以及致癌性Ras诱导的细胞转化的调控中起关键作用。将Ras激活与c-Jun磷酸化偶联的信号转导通路仍部分不明。在此我们表明，Ras效应器Rlf（一种小GTP酶Ral的鸟嘌呤核苷酸交换因子（GEF））的激活形式可诱导c-Jun丝氨酸63和73的磷酸化。此外，我们表明，RalGEF-Ral通路的抑制性突变体可消除生长因子诱导的、Ras介导的c-Jun磷酸化。这些结果表明，RalGEF-Ral通路在Ras依赖性c-Jun磷酸化中起主要作用。Ral依赖性c-Jun磷酸化的调控涉及JNK、一种仍不明的JNKK以及可能的Src。
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