title: A direct interaction between the large GTPase dynamin-2 and FAK regulates focal adhesion dynamics in response to active Src.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Hong
authors.initials: H
authors.lastname: Cao
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Mark A
authors.initials: MA
authors.lastname: McNiven
mesh_terms: D000818:Animals; D000906:Antibodies; D002448:Cell Adhesion; D002465:Cell Movement / Q000502:physiology*; D002966:Clathrin / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D034285:Dynamin II / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D022001:Focal Adhesions / Q000502:physiology*; D006801:Humans; D016023:Integrins / Q000378:metabolism / Q000502:physiology; D010766:Phosphorylation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D034622:RNA Interference; D034741:RNA, Small Interfering; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D000906:Antibodies; D002966:Clathrin; D003598:Cytoskeletal Proteins; D016023:Integrins; D034741:RNA, Small Interfering; D051417:Focal Adhesion Kinase 1; D019061:src-Family Kinases; D034285:Dynamin II