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.
机构:G. Daum, I. Eisenmann-Tappe, H-W. Fries, J. Troppmair and U.R. Rapp are at the Institute of Medical Radiobiology and Cell Biology, University of Würzburg, Versbacher Strasse 5
DAUM, G
;
EISENMANNTAPPE, I
论文数: 0引用数: 0
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机构:G. Daum, I. Eisenmann-Tappe, H-W. Fries, J. Troppmair and U.R. Rapp are at the Institute of Medical Radiobiology and Cell Biology, University of Würzburg, Versbacher Strasse 5
EISENMANNTAPPE, I
;
FRIES, HW
论文数: 0引用数: 0
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机构:G. Daum, I. Eisenmann-Tappe, H-W. Fries, J. Troppmair and U.R. Rapp are at the Institute of Medical Radiobiology and Cell Biology, University of Würzburg, Versbacher Strasse 5
FRIES, HW
;
TROPPMAIR, J
论文数: 0引用数: 0
h-index: 0
机构:G. Daum, I. Eisenmann-Tappe, H-W. Fries, J. Troppmair and U.R. Rapp are at the Institute of Medical Radiobiology and Cell Biology, University of Würzburg, Versbacher Strasse 5
TROPPMAIR, J
;
RAPP, UR
论文数: 0引用数: 0
h-index: 0
机构:G. Daum, I. Eisenmann-Tappe, H-W. Fries, J. Troppmair and U.R. Rapp are at the Institute of Medical Radiobiology and Cell Biology, University of Würzburg, Versbacher Strasse 5
机构:G. Daum, I. Eisenmann-Tappe, H-W. Fries, J. Troppmair and U.R. Rapp are at the Institute of Medical Radiobiology and Cell Biology, University of Würzburg, Versbacher Strasse 5
DAUM, G
;
EISENMANNTAPPE, I
论文数: 0引用数: 0
h-index: 0
机构:G. Daum, I. Eisenmann-Tappe, H-W. Fries, J. Troppmair and U.R. Rapp are at the Institute of Medical Radiobiology and Cell Biology, University of Würzburg, Versbacher Strasse 5
EISENMANNTAPPE, I
;
FRIES, HW
论文数: 0引用数: 0
h-index: 0
机构:G. Daum, I. Eisenmann-Tappe, H-W. Fries, J. Troppmair and U.R. Rapp are at the Institute of Medical Radiobiology and Cell Biology, University of Würzburg, Versbacher Strasse 5
FRIES, HW
;
TROPPMAIR, J
论文数: 0引用数: 0
h-index: 0
机构:G. Daum, I. Eisenmann-Tappe, H-W. Fries, J. Troppmair and U.R. Rapp are at the Institute of Medical Radiobiology and Cell Biology, University of Würzburg, Versbacher Strasse 5
TROPPMAIR, J
;
RAPP, UR
论文数: 0引用数: 0
h-index: 0
机构:G. Daum, I. Eisenmann-Tappe, H-W. Fries, J. Troppmair and U.R. Rapp are at the Institute of Medical Radiobiology and Cell Biology, University of Würzburg, Versbacher Strasse 5