Regulatory proteins of R-Ras, TC21/R-Ras2, and M-Ras/R-Ras3

被引:125
作者
Ohba, Y
Mochizuki, N
Yamashita, S
Chan, AM
Schrader, JW
Hattori, S
Nagashima, K
Matsuda, M
机构
[1] Int Med Ctr Japan, Res Inst, Dept Pathol, Shinjuku Ku, Tokyo 1828655, Japan
[2] Hokkaido Univ, Sch Med, Lab Mol & Cellular Pathol, Kita Ku, Sapporo, Hokkaido 0608638, Japan
[3] Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Div Biochem & Cellular Biol, Tokyo 1878502, Japan
[4] CUNY Mt Sinai Sch Med, Dernald H Ruttenberg Canc Ctr, New York, NY 10029 USA
[5] Univ British Columbia, Biomed Res Ctr, Vancouver, BC V6T 1Z3, Canada
关键词
D O I
10.1074/jbc.M000981200
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
We studied the regulation of three closely related members of Pas family G proteins, R-Ras, TC21 (also known as R-Ras2), and M-Ras (R-Ras3). Guanine nucleotide exchange of R-Ras and TC21 was promoted by RasGRF, C3G, CalDAG-GEFI, CalDAG-GEFII (RasGRP), and CalDAG-GEFIII both in 293T cells and in vitro. By contrast, guanine nucleotide exchange of M-Ras was promoted by the guanine nucleotide exchange factors (GEFs) for the classical Pas (Ha-, K-, and N-), including mSos, RasGRF, CalDAG-GEFII, and CalDAG-GEFIII. GTPase-activating proteins (GAPs) for Pas, Gap1(m), p120 GAP, and NF-1 stimulated all of the R-Ras, TC21, and M-Ras proteins, whereas R-Ras GAP stimulated R-Ras and TC21 but not M-Ras. We did not find any remarkable difference in the subcellular localization of R-Ras, TC21, or M-Ras when these were expressed with a green fluorescent protein tag in 293T cells and MDCK cells. In conclusion, TC21 and R-Ras were regulated by the same GEFs and GAPs, whereas M-Ras was regulated as the classical Ras.
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页码:20020 / 20026
页数:7
相关论文
共 48 条
[1]   The structural basis of the activation of Ras by Sos [J].
Boriack-Sjodin, PA ;
Margarit, SM ;
Bar-Sagi, D ;
Kuriyan, J .
NATURE, 1998, 394 (6691) :337-343
[2]   Ras-like GTPases [J].
Bos, JL .
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER, 1997, 1333 (02) :M19-M31
[3]  
Buchsbaum R, 1996, MOL CELL BIOL, V16, P4888
[4]   HUMAN ONCOGENE OF THE RAS SUPERFAMILY UNMASKED BY EXPRESSION CDNA CLONING [J].
CHAN, AML ;
MIKI, T ;
MEYERS, KA ;
AARONSON, SA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (16) :7558-7562
[5]   Endomembrane trafficking of Ras: The CAAX motif targets proteins to the ER and Golgi [J].
Choy, E ;
Chiu, VK ;
Silletti, J ;
Feoktistov, M ;
Morimoto, T ;
Michaelson, D ;
Ivanov, IE ;
Philips, MR .
CELL, 1999, 98 (01) :69-80
[6]  
Clark GJ, 1996, ONCOGENE, V12, P169
[7]  
COX AD, 1994, ONCOGENE, V9, P3281
[8]   Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP [J].
de Rooij, J ;
Zwartkruis, FJT ;
Verheijen, MHG ;
Cool, RH ;
Nijman, SMB ;
Wittinghofer, A ;
Bos, JL .
NATURE, 1998, 396 (6710) :474-477
[9]   PDZ-GEF1, a guanine nucleotide exchange factor specific for Rap1 and Rap2 [J].
de Rooij, J ;
Boenink, NM ;
van Triest, M ;
Cool, RH ;
Wittinghofer, A ;
Bos, JL .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (53) :38125-38130
[10]   RasGRP, a Ras guanyl nucleotide-releasing protein with calcium- and diacylglycerol-binding motifs [J].
Ebinu, JO ;
Bottorff, DA ;
Chan, EYW ;
Stang, SL ;
Dunn, RJ ;
Stone, JC .
SCIENCE, 1998, 280 (5366) :1082-1086