Role of Raf-1 conserved region 2 in regulation of Ras-dependent Raf-1 activation

被引:11
作者
Sendoh, H [1 ]
Hu, CD [1 ]
Wu, DM [1 ]
Song, CH [1 ]
Yamawaki-Kataoka, Y [1 ]
Kotani, J [1 ]
Okada, T [1 ]
Shima, F [1 ]
Kariya, K [1 ]
Kataoka, T [1 ]
机构
[1] Kobe Univ, Sch Med, Dept Physiol 2, Chuo Ku, Kobe, Hyogo 6500017, Japan
关键词
Ras; Raf; cysteine-rich domain; protein kinase C; TPA; phosphorylation;
D O I
10.1006/bbrc.2000.2674
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
Full activation of Raf-l requires the interaction of its CRD with Has. The serine/threonine-rich region, CR2, of Raf-l was implicated in Raf-l regulation, but the underlying mechanism was unclear. Here we show that CRD loses its Ras-binding activity when expressed in connection with CR2, suggesting that CR2 masks CRD. This masking effect is abolished by substitution of Asp or Ala for Ser-259, a growth factor- and TPA-induced phosphorylation site in CR2. Treatment of COS-7 cells expressing Ha-Ras(Val-12) and Raf-l with TPA enhances the Ha-Ras(Val-12)-dependent Raf-l kinase activity. In contrast, the Ha-Ras(Val-12)-dependent activities of the Raf-1(S259D) and Raf-1(S259A) mutants are comparable to that of wild-type Raf-l stimulated by both Ha-Ras(Val-12) and TPA and cannot be further stimulated by TPA treatment. These results suggest that the in vivo phosphorylation of Ser-259 may comprise a crucial step for Ras-dependent Raf-l activation by unmasking CRD and promoting its association with Ras. (C) 2000 Academic Press.
引用
收藏
页码:596 / 602
页数:7
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