The tumor suppressor hamartin enhances Dbl protein transforming activity through interaction with ezrin

Marzia Ognibene, Cristina Vanni, Daniela Segalerba, Patrizia Mancini, Elisa Merello, Maria Rosaria Torrisi, Maria Carla Bosco, Luigi Varesio, Alessandra Eva

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The Rho guanine nucleotide exchange factor (GEF) Dbl binds to the N-terminal region of ezrin, a member of the ERM (ezrin, radixin, moesin) proteins known to function as linkers between the plasma membrane and the actin cytoskeleton. Here we have characterized the interaction between ezrin and Dbl. We show that binding of Dbl with ezrin involves positively charged amino acids within the region of the pleckstrin homology (PH) domain comprised between β1 and β2 sheets. In addition, we show that Dbl forms a complex with the tuberous sclerosis-1 (TSC-1) gene product hamartin and with ezrin. We demonstrate that hamartin and ezrin are both required for activation of Dbl. In fact, the knock-down of ezrin and hamartin, as well as the expression of a mutant hamartin, unable to bind ezrin, inhibit Dbl transforming and exchange activity. These results suggest that Dbl is regulated by hamartin through association with ezrin.

Original languageEnglish
Pages (from-to)29973-29983
Number of pages11
JournalJournal of Biological Chemistry
Volume286
Issue number34
DOIs
Publication statusPublished - Aug 26 2011

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Tumors
Neoplasms
Proteins
Rho Guanine Nucleotide Exchange Factors
tuberous sclerosis complex 1 protein
ezrin
Cell membranes
Actin Cytoskeleton
Actins
Genes
Chemical activation
Cell Membrane
Association reactions
Amino Acids

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

The tumor suppressor hamartin enhances Dbl protein transforming activity through interaction with ezrin. / Ognibene, Marzia; Vanni, Cristina; Segalerba, Daniela; Mancini, Patrizia; Merello, Elisa; Torrisi, Maria Rosaria; Bosco, Maria Carla; Varesio, Luigi; Eva, Alessandra.

In: Journal of Biological Chemistry, Vol. 286, No. 34, 26.08.2011, p. 29973-29983.

Research output: Contribution to journalArticle

Ognibene, Marzia ; Vanni, Cristina ; Segalerba, Daniela ; Mancini, Patrizia ; Merello, Elisa ; Torrisi, Maria Rosaria ; Bosco, Maria Carla ; Varesio, Luigi ; Eva, Alessandra. / The tumor suppressor hamartin enhances Dbl protein transforming activity through interaction with ezrin. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 34. pp. 29973-29983.
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AU - Bosco, Maria Carla

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