Role of scaffold protein afadin dilute domain-interacting protein (ADIP) in platelet-derived growth factor-induced cell movement by activating Rac protein through Vav2 protein.
Cell movement is an important cellular function not only in physiological but also in pathological conditions. Although numerous studies have been conducted to reveal the mechanism of cell movement, the full picture has yet to be depicted, likely due to the complex features of cell movement. We show here that the scaffold protein afadin dilute domain-interacting protein (ADIP), an afadin-binding protein, is involved in the regulation of cell movement. ADIP localized at the leading edge of moving cells in response to platelet-derived growth factor (PDGF) and was required for the formation of the leading edge and the promotion of cell movement. Impaired cell movement observed in ADIP knockdown cells was not rescued by expression of an ADIP mutant that is incapable of binding to afadin, leading to the notion that the function of ADIP in moving cells depends on its interaction with afadin. Knockdown of ADIP as well as knockdown of afadin inhibited the activation of the small G protein Rac, which is important for the formation of the leading edge and the promotion of cell movement. Furthermore, ADIP interacted with Vav2, a GDP/GTP exchange factor for Rac, in a Src phosphorylation-dependent manner, suggesting that ADIP mediates the activation of Rac through Vav2. These results indicate that ADIP plays an essential role in PDGF-induced cell movement by interacting with afadin and Vav2 and regulating the activation of Rac.
Division of Molecular and Cellular Biology, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Hyogo 650-0017, Japan.
Yuri
Y
Fukumoto
Souichi
S
Kurita
Yoshimi
Y
Takai
Hisakazu
H
Ogita
D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002465:Cell Movement / Q000187:drug effects; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism; D047468:Immunoprecipitation; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D008869:Microtubule-Associated Proteins; D041681:NIH 3T3 Cells; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011485:Protein Binding; D051567:Proto-Oncogene Proteins c-vav / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D020662:Guanine Nucleotide Exchange Factors; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D010982:Platelet-Derived Growth Factor; D051567:Proto-Oncogene Proteins c-vav; D034741:RNA, Small Interfering; C472295:Ssx2ip protein, mouse; C490565:Vav2 protein, mouse; C108835:afadin; D020744:rac GTP-Binding Proteins