title: Phosphorylation of Ser 402 impedes phosphatase activity of slingshot 1.
abstract: By using mass spectrometry, we have identified Ser 402 as a new phosphorylation site within the catalytic domain of human slingshot 1 (SSH1). Phosphorylation at this site inhibits substrate binding and, thus, phosphatase activity in vitro, resulting in enrichment of phosphorylated cofilin in monolayer cell culture. We further demonstrate that protein kinase D (PKD) is upstream from Ser 402 phosphorylation. Accordingly, expression of active PKD in Drosophila phenotypically mimics the loss of SSH activity by inducing accumulation of phosphorylated cofilin and filamentous actin. We thus identify a universal mechanism by which PKD controls SSH1 phosphatase activity.
authors.affiliation: Institute for Cell Biology and Immunology, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Barišić
authors.forename: Anja C
authors.initials: AC
authors.lastname: Nagel
authors.forename: Mirita
authors.initials: M
authors.lastname: Franz-Wachtel
authors.forename: Boris
authors.initials: B
authors.lastname: Macek
authors.forename: Anette
authors.initials: A
authors.lastname: Preiss
authors.forename: Gisela
authors.initials: G
authors.lastname: Link
authors.forename: Dieter
authors.initials: D
authors.lastname: Maier
authors.forename: Angelika
authors.initials: A
authors.lastname: Hausser
mesh_terms: D051339:Actin Depolymerizing Factors / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D004789:Enzyme Activation / Q000235:genetics; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D011493:Protein Kinase C / Q000737:chemistry / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D012694:Serine / Q000378:metabolism*
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D011993:Recombinant Fusion Proteins; D012694:Serine; C089212:protein kinase D; D011493:Protein Kinase C; D010749:Phosphoprotein Phosphatases; C484329:SSH1 protein, human