Gα13 regulation of proto-Dbl signaling

Cristina Vanni, Patrizia Mancini, Catherine Ottaviano, Marzia Ognibene, Alessia Parodi, Elisa Merello, Chiara Russo, Luigi Varesio, Yi Zheng, Maria Rosaria Torrisi, Alessandra Eva

Research output: Contribution to journalArticle

Abstract

Rho family GTPases play important roles in the regulation of intracellular signals induced by activated heterotrimeric G proteins of the α12/13 family. The α12/13 subunits activate Rho GTPases through direct binding to a group of Rho guanine nucleotide exchange factors (GEFs) characterized by the presence of a G protein signaling-like (RGL) domain. The Rho GEF proto-Dbl, that does not contain a RGL domain, was also found to link Gα12/13 signals to Rho. We have explored the effects of activated Gα13 and Gα13-associated G protein-coupled receptor (GPCR) agonists on proto-Dbl regulation. We show that activated Gα13, but not Gα12 or Gαq, induces translocation of proto-Dbl to the cell membrane with consequent enlargement of cell body and membrane ruffling. These effects were evident also when Gα13-associated GPCR agonists were used on cells expressing proto-Dbl and were accompanied by the activation of Cdc42 and RhoA GTPases and further downstream effector JNK and p38 kinases. Moreover, we show that both activated Gα13 and GPCR agonists stimulate proto-Dbl interaction with ezrin to promote ezrin translocation to the plasma membrane. These results suggest a mechanism by which proto-Dbl and its effector pathways are regulated by Gα13-mediated signals through association with ezrin.

Original languageEnglish
Pages (from-to)2058-2070
Number of pages13
JournalCell Cycle
Volume6
Issue number16
Publication statusPublished - Aug 15 2007

Fingerprint

G12-G13 GTP-Binding Protein alpha Subunits
G-Protein-Coupled Receptors
Rho Guanine Nucleotide Exchange Factors
rho GTP-Binding Proteins
GTP Phosphohydrolases
Cell Membrane
Cell membranes
Cells
MAP Kinase Kinase 4
Heterotrimeric GTP-Binding Proteins
GTP-Binding Proteins
Phosphotransferases
Chemical activation
Association reactions
Membranes
ezrin

Keywords

  • Ezrin
  • GPCR-agonists
  • GTPases
  • Proto-Dbl

ASJC Scopus subject areas

  • Cell Biology
  • Biochemistry
  • Molecular Biology
  • Medicine(all)

Cite this

Vanni, C., Mancini, P., Ottaviano, C., Ognibene, M., Parodi, A., Merello, E., ... Eva, A. (2007). Gα13 regulation of proto-Dbl signaling. Cell Cycle, 6(16), 2058-2070.

Gα13 regulation of proto-Dbl signaling. / Vanni, Cristina; Mancini, Patrizia; Ottaviano, Catherine; Ognibene, Marzia; Parodi, Alessia; Merello, Elisa; Russo, Chiara; Varesio, Luigi; Zheng, Yi; Torrisi, Maria Rosaria; Eva, Alessandra.

In: Cell Cycle, Vol. 6, No. 16, 15.08.2007, p. 2058-2070.

Research output: Contribution to journalArticle

Vanni, C, Mancini, P, Ottaviano, C, Ognibene, M, Parodi, A, Merello, E, Russo, C, Varesio, L, Zheng, Y, Torrisi, MR & Eva, A 2007, 'Gα13 regulation of proto-Dbl signaling', Cell Cycle, vol. 6, no. 16, pp. 2058-2070.
Vanni C, Mancini P, Ottaviano C, Ognibene M, Parodi A, Merello E et al. Gα13 regulation of proto-Dbl signaling. Cell Cycle. 2007 Aug 15;6(16):2058-2070.
Vanni, Cristina ; Mancini, Patrizia ; Ottaviano, Catherine ; Ognibene, Marzia ; Parodi, Alessia ; Merello, Elisa ; Russo, Chiara ; Varesio, Luigi ; Zheng, Yi ; Torrisi, Maria Rosaria ; Eva, Alessandra. / Gα13 regulation of proto-Dbl signaling. In: Cell Cycle. 2007 ; Vol. 6, No. 16. pp. 2058-2070.
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