Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 373, Issue 5, pp 333–341

Gef10—the third member of a Rho-specific guanine nucleotide exchange factor subfamily with unusual protein architecture

Original Article

Abstract

According to cDNA sequence homologies, Gef10 is related to the Rho-specific guanine nucleotide exchange factors GrinchGEF and p164-RhoGEF. Like these GEFs, Gef10 exhibits only weak homology to known pleckstrin homology domains, but contains a putative WD40-like domain. As detected by RT-PCR, Gef10 is transcribed in at least two splice variants in different human tissues. Although the Gef10 sequence contains two putative transmembrane segments, recombinantly expressed Gef10 displays a cytosolic localisation. As detected by guanine nucleotide exchange activity assay, precipitation assay of GTP-bound Rho proteins and serum response element dependent gene transcription Gef10 activates RhoA-C, but not Rac1 or Cdc42. In the reporter gene assay, Gef10 preferentially activated RhoB. When expressed in NIH3T3 cells, Gef10 induced actin stress fibre, but not lamellipodia or filopodia formation. We conclude that Gef10 is the third member of a Rho-specific GEF family with unusual protein architecture.

Keywords

Dbl family Guanine nucleotide exchange factors Rho proteins Signal transduction 

Abbreviations

DH

Dbl homology

EGFP

Enhanced green fluorescent protein

GEF

Guanine nucleotide exchange factor

GST

Glutathione S-transferase

HA

Hemagglutinin

PH

Pleckstrin homology

SRE

Serum response element

SRF

Serum response factor

TRITC

Tetramethylrhodamine isothiocyanate

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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  1. 1.Institut für Experimentelle und Klinische Pharmakologie und ToxikologieUniversität HeidelbergMannheimGermany

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