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 [J].

Berman, DM ;

Gilman, AG .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (03) :1269-1272

[2] PROTEINS REGULATING RAS AND ITS RELATIVES [J].

BOGUSKI, MS ;

MCCORMICK, F .

NATURE, 1993, 366 (6456) :643-654

[3] G-ALPHA(12) AND G-ALPHA(13) STIMULATE RHO-DEPENDENT STRESS FIBER FORMATION AND FOCAL ADHESION ASSEMBLY [J].

BUHL, AM ;

JOHNSON, NL ;

DHANASEKARAN, N ;

JOHNSON, GL .

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 [J].

COSO, OA ;

CHIARIELLO, M ;

YU, JC ;

TERAMOTO, H ;

CRESPO, P ;

XU, NG ;

MIKI, T ;

GUTKIND, JS .

CELL, 1995, 81 (07) :1137-1146

[5] Protein-protein interactions: PDZ domain networks [J].

Fanning, AS ;

Anderson, JM .

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 [J].

Fromm, C ;

Coso, OA ;

Montaner, S ;

Xu, NZ ;

Gutkind, JS .

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 [J].

Fukuhara, S ;

Marinissen, MJ ;

Chiariello, M ;

Gutkind, JS .

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 [J].

Fukuhara, S ;

Murga, C ;

Zohar, M ;

Igishi, T ;

Gutkind, JS .

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 [J].

Häcker, U ;

Perrimon, N .

GENES & DEVELOPMENT, 1998, 12 (02) :274-284

[10]

HART MJ, 1994, J BIOL CHEM, V269, P62

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