A direct interaction between the large GTPase dynamin-2 and FAK regulates focal adhesion dynamics in response to active Src

Yu Wang, Hong Cao, Jing Chen, Mark A Mc Niven

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Tumor cell migration is supported in part by the cyclic formation and disassembly of focal adhesions (FAs); however, the mechanisms that regulate this process are not fully defined. The large guanosine 5′-triphosphatase dynamin (Dyn) plays an important role in FA dynamics and is activated by tyrosine phosphorylation. Using a novel antibody specific to phospho-dynamin (pDyn-Tyr-231), we found that Dyn2 is phosphorylated at FAs by Src kinase and is recruited to FAs by a direct interaction with the 4.1/ezrin/radizin/moesin domain of focal adhesion kinase (FAK), which functions as an adaptor between Src and Dyn2 to facilitate Dyn2 phosphorylation. This Src-FAK-Dyn2 trimeric complex is essential for FA turnover, as mutants disrupting the formation of this complex inhibit FA disassembly. Importantly, phosphoactivated Dyn2 promotes FA turnover by mediating the endocytosis of integrins in a clathrin-dependent manner. This study defines a novel mechanism of how Dyn2 functions as a downstream effector of FAK-Src signaling in turning over FAs.

Original languageEnglish (US)
Pages (from-to)1529-1538
Number of pages10
JournalMolecular Biology of the Cell
Volume22
Issue number9
DOIs
StatePublished - May 1 2011

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Dynamin II
Focal Adhesion Protein-Tyrosine Kinases
Focal Adhesions
GTP Phosphohydrolases
Dynamins
Phosphorylation
Phospho-Specific Antibodies
Clathrin
src-Family Kinases
Guanosine
Endocytosis
Integrins
Cell Movement
Tyrosine

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

A direct interaction between the large GTPase dynamin-2 and FAK regulates focal adhesion dynamics in response to active Src. / Wang, Yu; Cao, Hong; Chen, Jing; Mc Niven, Mark A.

In: Molecular Biology of the Cell, Vol. 22, No. 9, 01.05.2011, p. 1529-1538.

Research output: Contribution to journalArticle

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