Rho GTPases, which are activated by specific guanine-nucleotide exchange factors (GEFs), play pivotal roles in several cellular functions. We identified a recently cloned human cDNA, namely KIAA0337, encoding a protein containing 1510 amino acids (p164). It contains a RhoGEF-specific Dbl homology (DH) domain but lacks their typical pleckstrin homology domain. The expression of the mRNA encoding p164 was found to be at least 4-fold higher in the heart than in other tissues. Recombinant p164 interacted with and induced GDP/GTP exchange at RhoA but not at Rac1 or Cdc42. p164-ΔC and p164-ΔN are p164 mutants that are truncated at the C- and N-termini respectively but contain the DH domain. In contrast with the full-length p164, expression of p164-ΔC and p164-ΔN strongly induced actin stress fibre formation and activated serum response factor-mediated and Rho-dependent gene transcription. Interestingly, p164-ΔN2, a mutant containing the C-terminus but having a defective DH domain, bound to p164-ΔC and suppressed the p164-ΔC-induced gene transcription. Overexpression of the full-length p164 inhibited M3 muscarinic receptor-induced gene transcription, whereas co-expression with Gβ1γ2 dimers induced transcriptional activity. It is concluded that p164-RhoGEF is a Rho-specific GEF with novel structural and regulatory properties and predominant expression in the heart. Apparently, its N- and C-termini interact with each other, thereby inhibiting its GEF activity.
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September 2002
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Research Article|
September 15 2002
A mammalian Rho-specific guanine-nucleotide exchange factor (p164-RhoGEF) without a pleckstrin homology domain
Ulrich RÜMENAPP;
Ulrich RÜMENAPP
1
∗Institut für Pharmakologie, Universitätsklinikum Essen, Hufelandstrasse 55, D-45122 Essen, Germany,
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Andrea FREICHEL-BLOMQUIST;
Andrea FREICHEL-BLOMQUIST
1
∗Institut für Pharmakologie, Universitätsklinikum Essen, Hufelandstrasse 55, D-45122 Essen, Germany,
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Burkhard WITTINGHOFER;
Burkhard WITTINGHOFER
∗Institut für Pharmakologie, Universitätsklinikum Essen, Hufelandstrasse 55, D-45122 Essen, Germany,
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Karl H. JAKOBS;
Karl H. JAKOBS
∗Institut für Pharmakologie, Universitätsklinikum Essen, Hufelandstrasse 55, D-45122 Essen, Germany,
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Thomas WIELAND
Thomas WIELAND
2
†Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany
2To whom correspondence should be addressed (e-mail wieland@uke.uni-hamburg.de).
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Publisher: Portland Press Ltd
Received:
April 24 2002
Revision Received:
June 07 2002
Accepted:
June 19 2002
Accepted Manuscript online:
June 19 2002
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2002
2002
Biochem J (2002) 366 (3): 721–728.
Article history
Received:
April 24 2002
Revision Received:
June 07 2002
Accepted:
June 19 2002
Accepted Manuscript online:
June 19 2002
Citation
Ulrich RÜMENAPP, Andrea FREICHEL-BLOMQUIST, Burkhard WITTINGHOFER, Karl H. JAKOBS, Thomas WIELAND; A mammalian Rho-specific guanine-nucleotide exchange factor (p164-RhoGEF) without a pleckstrin homology domain. Biochem J 15 September 2002; 366 (3): 721–728. doi: https://doi.org/10.1042/bj20020654
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