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Regulation of RHOV signaling by interaction with SH3 domain-containing adaptor proteins and phosphorylation by PKA.
Harlin, Eka Wahyuni; Ito, Takuya; Nakano, Shun; Morikawa, Kohei; Sato, Katsuya; Nishikawa, Masashi; Nakamura, Katsuyuki; Nagaoka, Hitoshi; Nagase, Takahiro; Ueda, Hiroshi.
Afiliación
  • Harlin EW; United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Yanagido1-1, Gifu, 501-1193, Japan.
  • Ito T; Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, Yanagido 1-1, Gifu, 501-1193, Japan.
  • Nakano S; United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Yanagido1-1, Gifu, 501-1193, Japan.
  • Morikawa K; United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Yanagido1-1, Gifu, 501-1193, Japan.
  • Sato K; Department of Molecular Pathobiochemistry, Gifu University Graduate School of Medicine, Yanagido 1-1, Gifu, 501-1193, Japan.
  • Nishikawa M; United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Yanagido1-1, Gifu, 501-1193, Japan.
  • Nakamura K; Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, Yanagido 1-1, Gifu, 501-1193, Japan.
  • Nagaoka H; Department of Molecular Pathobiochemistry, Gifu University Graduate School of Medicine, Yanagido 1-1, Gifu, 501-1193, Japan; Center for One Medicine Innovative Translational Research (COMIT), Gifu University, 1-1 Yanagido, Gifu, Gifu, 501-1193, Japan.
  • Nagase T; Kazusa DNA Research Institute, Chiba, Japan.
  • Ueda H; United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Yanagido1-1, Gifu, 501-1193, Japan; Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, Yanagido 1-1, Gifu, 501-1193, Japan; Center for One Medicine Innovative Translati
Biochem Biophys Res Commun ; 728: 150325, 2024 Oct 08.
Article en En | MEDLINE | ID: mdl-38959529
ABSTRACT
RHOV and RHOU are considered atypical Rho-family small GTPases because of the existence of N- and C-terminal extension regions, abnormal GDP/GTP cycling, and post-translational modification. Particularly, RHOV and RHOU both have a proline-rich (PR) motif in the N-terminal region. It has been reported that the PR motif of RHOU interacts with GRB2, a SH3 domain-containing adaptor protein, and regulates its activity through EGF receptor signaling. However, it is unknown whether RHOV, like RHOU, interacts with SH3 domain-containing adaptor proteins. In this study, we investigated the interactions between RHOV and SH3 domain-containing adaptor proteins, including GRB2 and NCK2. The RHOV-induced serum response factor (SRF)-dependent gene transcriptional activity was attenuated in cells co-expressing either GRB2 or NCK2 compared to cells expressing RHOV alone. From the results of experiments using various gene mutants of RHOV and GRB2, it appears that the PR motif of the N-terminal region of RHOV is the crucial binding site for the SH3 domain-containing proteins. Furthermore, we found that Ser25 in the N-terminal region of RHOV is phosphorylated by PKA and that its phosphorylation is suppressed by interaction with NCK2 but not GRB2. We have found a novel regulatory mechanism for the phosphorylation of RHOV and its interaction with SH3 domain-containing adaptor proteins.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Proteínas Quinasas Dependientes de AMP Cíclico / Dominios Homologos src / Proteínas Adaptadoras Transductoras de Señales / Proteína Adaptadora GRB2 Límite: Humans Idioma: En Revista: Biochem Biophys Res Commun Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Proteínas Quinasas Dependientes de AMP Cíclico / Dominios Homologos src / Proteínas Adaptadoras Transductoras de Señales / Proteína Adaptadora GRB2 Límite: Humans Idioma: En Revista: Biochem Biophys Res Commun Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos