Coupling of Ras and Rac guanosine triphosphatases through the Ras exchanger Sos

被引:386
作者
Nimnual, AS [1 ]
Yatsula, BA [1 ]
Bar-Sagi, D [1 ]
机构
[1] SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA
关键词
D O I
10.1126/science.279.5350.560
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The Son of Sevenless (Sos) proteins control receptor-mediated activation of Ras by catalyzing the exchange of guanosine diphosphate for guanosine triphosphate on Ras. The NH2-terminal region of Sos contains a Dbl homology (DH) domain in tandem with a pleckstrin homology (PH) domain. In COS-1 cells, the DH domain of Sos stimulated guanine nucleotide exchange on Rac but not Cdc42 in vitro and in vivo. The tandem DH-PH domain of Sos (DH-PH-Sos) was defective in Rac activation but regained Rac stimulating activity when it was coexpressed with activated Ras, Ras-mediated activation of DH-PH-Sos did not require activation of mitogen-activated protein kinase but it was dependent on activation of phosphoinositide 3-kinase. These results reveal a potential mechanism for coupling of Ras and Rac signaling pathways.
引用
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页码:560 / 563
页数:4
相关论文
共 30 条
  • [1] THE SOS (SON OF SEVENLESS) PROTEIN
    BARSAGI, D
    [J]. TRENDS IN ENDOCRINOLOGY AND METABOLISM, 1994, 5 (04) : 165 - 169
  • [2] BROEK D, COMMUNICATION
  • [3] The Dbl family of oncogenes
    Cerione, RA
    Zheng, Y
    [J]. CURRENT OPINION IN CELL BIOLOGY, 1996, 8 (02) : 216 - 222
  • [4] The role of the PH domain in the signal-dependent membrane targeting of Sos
    Chen, RH
    CorbalanGarcia, S
    BarSagi, D
    [J]. EMBO JOURNAL, 1997, 16 (06) : 1351 - 1359
  • [5] THE SMALL GTP-BINDING PROTEINS RAC1 AND CDC42 REGULATE THE ACTIVITY OF THE JNK/SAPK SIGNALING PATHWAY
    COSO, OA
    CHIARIELLO, M
    YU, JC
    TERAMOTO, H
    CRESPO, P
    XU, NG
    MIKI, T
    GUTKIND, JS
    [J]. CELL, 1995, 81 (07) : 1137 - 1146
  • [6] Role of substrates and products of PI3-kinase in regulating activation of Rac-related guanosine triphosphatases by Vav
    Han, JW
    Luby-Phelps, K
    Das, B
    Shu, XD
    Xia, Y
    Mosteller, RD
    Krishna, UM
    Falck, JR
    White, MA
    Broek, D
    [J]. SCIENCE, 1998, 279 (5350) : 558 - 560
  • [7] Stimulation of membrane ruffling and MAP kinase activation by distinct effectors of RAS
    Joneson, T
    White, MA
    Wigler, MH
    BarSagi, D
    [J]. SCIENCE, 1996, 271 (5250) : 810 - 812
  • [8] Ras effectors and their role in mitogenesis and oncogenesis
    Joneson, T
    BarSagi, D
    [J]. JOURNAL OF MOLECULAR MEDICINE-JMM, 1997, 75 (08): : 587 - 593
  • [9] RAC regulation of actin polymerization and proliferation by a pathway distinct from Jun kinase
    Joneson, T
    McDonough, M
    BarSagi, D
    VanAelst, L
    [J]. SCIENCE, 1996, 274 (5291) : 1374 - 1376
  • [10] THE RAS SIGNAL-TRANSDUCTION PATHWAY
    KHOSRAVIFAR, R
    DER, CJ
    [J]. CANCER AND METASTASIS REVIEWS, 1994, 13 (01) : 67 - 89