ノズミ　モトヒロ   野住　素広    所属   新潟薬科大学  医療技術学部 臨床検査学科    職種   教授
言語種別	英語
発行・発表の年月	2003/06/15
形態種別	論文 - 研究論文（学術雑誌）
査読	査読あり
標題	IRSp53 is colocalised with WAVE2 at the tips of protruding lamellipodia and filopodia independently of Mena.
執筆形態	その他 - 指定なし
掲載誌名	Journal of cell science
掲載区分	国外
巻・号・頁	116(Pt 12),pp.2577-83
著者・共著者	Hiroyuki Nakagawa,Hiroaki Miki,Motohiro Nozumi,Tadaomi Takenawa,Shigeaki Miyamoto,Jürgen Wehland,J Victor Small
概要	The insulin receptor tyrosine kinase substrate p53 (IRSp53) links Rac and WAVE2 and has been implicated in lamellipodia protrusion. Recently, however, IRSp53 has been reported to bind to both Cdc42 and Mena to induce filopodia. To shed independent light on IRSp53 function we determined the localisations and dynamics of IRSp53 and WAVE2 in B16 melanoma cells. In cells spread well on a laminin substrate, IRSp53 was localised by antibody labelling at the tips of both lamellipodia and filopodia. The same localisation was observed in living cells with IRSp53 tagged with enhanced green florescence protein (EGFP-IRSp53), but only during protrusion. From the transfection of deletion mutants the N-terminal region of IRSp53, which binds active Rac, was shown to be responsible for its localisation. Although IRSp53 has been reported to regulate filopodia formation with Mena, EGFP-IRSp53 showed the same localisation in MVD7 Ena/VASP (vasodilator stimulated phosphoprotein) family deficient cells. WAVE2 tagged with DsRed1 colocalised with EGFP-IRSp53 at the tips of protruding lamellipodia and filopodia and, in double-transfected cells, the IRSp53 signal in filopodia decreased before that of WAVE2 during retraction. These results suggest an alternative modulatory role for IRSp53 in the extension of both filopodia and lamellipodia, through WAVE2.
ISSN	0021-9533
PMID	12734400