Leukemia-associated Rho guanine nucleotide exchange factor (LARG) links heterotrimeric G proteins of the G12 family to Rho

被引：195

作者：

Fukuhara, S ^{[1
]}

Chikumi, H ^{[1
]}

Gutkind, JS ^{[1
]}

机构：

[1] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA

来源：

FEBS LETTERS | 2000年 / 485卷 / 2-3期

关键词：

Rho; G protein; Ras; signal transduction; G protein-coupled receptor;

D O I：

10.1016/S0014-5793(00)02224-9

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：

A putative guanine nucleotide exchange factor (GEF), termed leukemia-associated RhoGEF (LARG), was recently identified upon fusion to the coding sequence of the MLL gene in acute myeloid leukemia. Although the function of LARG is still unknown, it exhibits a number of structural domains suggestive of a role in signal transduction, including a PDZ domain, a LH/ RGS domain, and a Dbl homology/pleckstrin homology domain. Here, we show that LARG can activate Rho in vivo. Furthermore, we present evidence that LARG is an integral component of a novel biochemical route whereby G protein-coupled receptors (GPCRs) and heterotrimeric G proteins of the Gait family stimulate Rho-dependent signaling pathways. (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.

引用

页码：183 / 188

页数：6

共 27 条

[1] Mammalian RGS proteins: Barbarians at the gate
Berman, DM
Gilman, AG
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (03) : 1269 - 1272
[2] PROTEINS REGULATING RAS AND ITS RELATIVES
BOGUSKI, MS
MCCORMICK, F
[J]. NATURE, 1993, 366 (6456) : 643 - 654
[3] G-ALPHA(12) AND G-ALPHA(13) STIMULATE RHO-DEPENDENT STRESS FIBER FORMATION AND FOCAL ADHESION ASSEMBLY
BUHL, AM
JOHNSON, NL
DHANASEKARAN, N
JOHNSON, GL
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (42) : 24631 - 24634
[4] 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
[5] Protein-protein interactions: PDZ domain networks
Fanning, AS
Anderson, JM
[J]. CURRENT BIOLOGY, 1996, 6 (11) : 1385 - 1388
[6] The small GTP-binding protein Rho links G protein-coupled receptors and G alpha(12) to the serum response element and to cellular transformation
Fromm, C
Coso, OA
Montaner, S
Xu, NZ
Gutkind, JS
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (19) : 10098 - 10103
[7] Signaling from G protein-coupled receptors to ERK5/big MAPK 1 involves Gαq and Gα12/13 families of heterotrimeric G proteins -: Evidence for the existence of a novel Ras and Rho-independent pathway
Fukuhara, S
Marinissen, MJ
Chiariello, M
Gutkind, JS
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (28) : 21730 - 21736
[8] A novel PDZ domain containing guanine nucleotide exchange factor links heterotrimeric G proteins to Rho
Fukuhara, S
Murga, C
Zohar, M
Igishi, T
Gutkind, JS
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (09) : 5868 - 5879
[9] DRhoGEF2 encodes a member of the Db1 family of oncogenes and controls cell shape changes during gastrulation in Drosophila
Häcker, U
Perrimon, N
[J]. GENES & DEVELOPMENT, 1998, 12 (02) : 274 - 284
[10] HART MJ, 1994, J BIOL CHEM, V269, P62

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