title: ERK signaling promotes cell motility by inducing the localization of myosin 1E to lamellipodial tips.
abstract: Signaling by extracellular signal-regulated kinase (ERK) plays an essential role in the induction of cell motility, but the precise mechanism underlying such regulation has remained elusive. We recently identified SH3P2 as a negative regulator of cell motility whose function is inhibited by p90 ribosomal S6 kinase (RSK)-mediated phosphorylation downstream of ERK. We here show that myosin 1E (Myo1E) is a binding partner of SH3P2 and that the interaction of the two proteins in the cytosol prevents the localization of Myo1E to the plasma membrane. Serum-induced phosphorylation of SH3P2 at Ser(202) by RSK results in dissociation of Myo1E from SH3P2 in the cytosol and the subsequent localization of Myo1E to the tips of lamellipodia mediated by binding of its TH2 domain to F-actin. This translocation of Myo1E is essential for lamellipodium extension and consequent cell migration. The ERK signaling pathway thus promotes cell motility through regulation of the subcellular localization of Myo1E.
authors: Department of Cell Regulation, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521, Japan Nagasaki University Research Centre for Genomic Instability and Carcinogenesis, Nagasaki 852-8523, Japan tani1211@nagasaki-u.ac.jp kohnom@nagasaki-u.ac.jp.
authors: Susumu
authors: S
authors: Tanimura
authors: Department of Cell Regulation, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521, Japan.
authors: Junya
authors: J
authors: Hashizume
authors: Department of Cell Regulation, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521, Japan.
authors: Naoya
authors: N
authors: Arichika
authors: Department of Cell Regulation, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521, Japan.
authors: Kazushi
authors: K
authors: Watanabe
authors: Department of Pharmacy Practice, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521, Japan Nagasaki University Research Centre for Genomic Instability and Carcinogenesis, Nagasaki 852-8523, Japan.
authors: Kaname
authors: K
authors: Ohyama
authors: Department of Cell Regulation, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521, Japan.
authors: Kohsuke
authors: K
authors: Takeda
authors: Department of Cell Regulation, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521, Japan tani1211@nagasaki-u.ac.jp kohnom@nagasaki-u.ac.jp.
authors: Michiaki
authors: 0000-0002-7644-0059
authors: M
authors: Kohno
mesh_terms: D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D020935:MAP Kinase Signaling System; D008954:Models, Biological; D024461:Myosin Type I / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D011392:Proline / Q000378:metabolism; D011485:Protein Binding; D000072417:Protein Domains; D021381:Protein Transport; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D011554:Pseudopodia / Q000378:metabolism*; D038744:Ribosomal Protein S6 Kinases, 90-kDa
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C118408:OSTF1 protein, human; D011506:Proteins; D010768:Phosphoserine; D011392:Proline; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C511011:MYO1E protein, human; D024461:Myosin Type I