THE SACCHAROMYCES-CEREVISIAE SDC25 C-DOMAIN GENE-PRODUCT OVERCOMES THE DOMINANT INHIBITORY ACTIVITY OF HA-RAS ASN-17

被引:62
作者
SCHWEIGHOFFER, F
CAI, H
CHEVALLIERMULTON, MC
FATH, I
COOPER, G
TOCOUE, B
机构
[1] RHONE POULENC RORER,13 QUAI JULES GUESDE,BP 14,F-94403 VITRY,FRANCE
[2] HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115
[3] HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,BOSTON,MA 02115
关键词
D O I
10.1128/MCB.13.1.39
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 carboxy-terminal part of the Saccharomyces cerevisiae SDC25 gene product (SDC25 C domain) can elicit activation of mammalian Ras proteins. Specifically, SDC25 C domain functions as an exchange factor for cellular Ras proteins in CHO cells. In this study, we used the dominant inhibitory Ha-Ras Asn-17 mutant and SDC25 C domain to further investigate the interaction between cellular Ras proteins and their putative endogenous guanine nucleotide-releasing factors. Transcription from the polyomavirus thymidine kinase gene (Py tk) promoter is strongly inhibited by the expression of Ha-Ras Asn-17 in NIH 3T3 cells. Coexpression of SDC25 C domain overcomes the negative effect of the Ras mutant on the Py tk promoter. On the other hand, transactivation of the Ras-responsive element of the Py tk promoter induced by SDC25 C domain is lost upon coexpression of increasing amounts of Ha-Ras Asn-17. In addition, coexpression of SDC25 C domain overcomes the inhibition of proliferation of NIH 3T3 cells caused by Ha-Ras Asn-17. These results are consistent with the idea that the Ha-Ras Asn-17 mutant functions by titrating an upstream activator of cellular Ras proteins.
引用
收藏
页码:39 / 43
页数:5
相关论文
共 42 条
  • [1] GUANOSINE TRIPHOSPHATASE ACTIVATING PROTEIN (GAP) INTERACTS WITH THE P21-RAS EFFECTOR BINDING DOMAIN
    ADARI, H
    LOWY, DR
    WILLUMSEN, BM
    DER, CJ
    MCCORMICK, F
    [J]. SCIENCE, 1988, 240 (4851) : 518 - 520
  • [2] THE NF1 LOCUS ENCODES A PROTEIN FUNCTIONALLY RELATED TO MAMMALIAN GAP AND YEAST IRA PROTEINS
    BALLESTER, R
    MARCHUK, D
    BOGUSKI, M
    SAULINO, A
    LETCHER, R
    WIGLER, M
    COLLINS, F
    [J]. CELL, 1990, 63 (04) : 851 - 859
  • [3] BARLAT I, IN PRESS ONCOGENE
  • [4] IDENTIFICATION OF MURINE HOMOLOGS OF THE DROSOPHILA SON OF SEVENLESS GENE - POTENTIAL ACTIVATORS OF RAS
    BOWTELL, D
    FU, P
    SIMON, M
    SENIOR, P
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (14) : 6511 - 6515
  • [5] THE C-TERMINAL PART OF A GENE PARTIALLY HOMOLOGOUS TO CDC25 GENE SUPPRESSES THE CDC25-5 MUTATION IN SACCHAROMYCES-CEREVISIAE
    BOYMARCOTTE, E
    DAMAK, F
    CAMONIS, J
    GARREAU, H
    JACQUET, M
    [J]. GENE, 1989, 77 (01) : 21 - 30
  • [6] THE SACCHAROMYCES-CEREVISIAE CDC25 GENE-PRODUCT REGULATES THE RAS/ADENYLATE CYCLASE PATHWAY
    BROEK, D
    TODA, T
    MICHAELI, T
    LEVIN, L
    BIRCHMEIER, C
    ZOLLER, M
    POWERS, S
    WIGLER, M
    [J]. CELL, 1987, 48 (05) : 789 - 799
  • [7] INSULIN STIMULATION OF GENE-EXPRESSION MEDIATED BY P21RAS ACTIVATION
    BURGERING, BMT
    MEDEMA, RH
    MAASSEN, JA
    VANDEWETERING, ML
    VANDEREB, AJ
    MCCORMICK, F
    BOS, JL
    [J]. EMBO JOURNAL, 1991, 10 (05) : 1103 - 1109
  • [8] HYDROLYSIS OF PHOSPHATIDYLCHOLINE IS STIMULATED BY RAS PROTEINS DURING MITOGENIC SIGNAL TRANSDUCTION
    CAI, H
    ERHARDT, P
    SZEBERENYI, J
    DIAZMECO, MT
    JOHANSEN, T
    MOSCAT, J
    COOPER, GM
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 1992, 12 (12) : 5329 - 5335
  • [9] EFFECT OF A DOMINANT INHIBITORY HA-RAS MUTATION ON MITOGENIC SIGNAL TRANSDUCTION IN NIH 3T3 CELLS
    CAI, H
    SZEBERENYI, J
    COOPER, GM
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 1990, 10 (10) : 5314 - 5323
  • [10] THE CYTOPLASMIC PROTEIN GAP IS IMPLICATED AS THE TARGET FOR REGULATION BY THE RAS GENE-PRODUCT
    CALES, C
    HANCOCK, JF
    MARSHALL, CJ
    HALL, A
    [J]. NATURE, 1988, 332 (6164) : 548 - 551