A mammalian Rho-specific guanine-nucleotide exchange factor (p164-RhoGEF) without a pleckstrin homology domain
In: Biochemical Journal, Jg. 366 (2002-09-15), S. 721-728
Online
unknown
Zugriff:
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-DeltaC and p164-DeltaN 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-DeltaC and p164-DeltaN strongly induced actin stress fibre formation and activated serum response factor-mediated and Rho-dependent gene transcription. Interestingly, p164-DeltaN2, a mutant containing the C-terminus but having a defective DH domain, bound to p164-DeltaC and suppressed the p164-DeltaC-induced gene transcription. Overexpression of the full-length p164 inhibited M(3) muscarinic receptor-induced gene transcription, whereas co-expression with Gbeta(1)gamma(2) 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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A mammalian Rho-specific guanine-nucleotide exchange factor (p164-RhoGEF) without a pleckstrin homology domain
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Autor/in / Beteiligte Person: | Jakobs, Karl ; Freichel-Blomquist, Andrea ; Wieland, Thomas ; Rümenapp, Ulrich ; Wittinghofer, Burkhard |
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Zeitschrift: | Biochemical Journal, Jg. 366 (2002-09-15), S. 721-728 |
Veröffentlichung: | Portland Press Ltd., 2002 |
Medientyp: | unknown |
ISSN: | 1470-8728 (print) ; 0264-6021 (print) |
DOI: | 10.1042/bj20020654 |
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