title: Phosphorylation of VASP by AMPK alters actin binding and occurs at a novel site.
abstract: Vasodilator-stimulated phosphoprotein (VASP) is an actin regulatory protein that functions in adhesion and migration. In epithelial cells, VASP participates in cell-cell adhesion. At the molecular level, VASP drives actin bundling and polymerization. VASP activity is primarily regulated by phosphorylation. Three physiologically relevant phosphorylation sites significantly reduce actin regulatory activity and are targeted by several kinases, most notable Abl and protein kinases A and G (PKA and PKG). AMP-dependent kinase (AMPK) is best characterized as a cellular sensor of ATP depletion, but also alters actin dynamics in epithelial cells and participates in cell polarity pathways downstream of LKB1. While little is known about how AMPK direct changes in actin dynamics, AMPK has been shown to phosphorylate VASP at one of these three well-characterized PKA/PKG phosphorylation sites. Here we show that phosphorylation of VASP by AMPK occurs at a novel site, serine 322, and that phosphorylation at this site alters actin filament binding. We also show that inhibition of AMPK activity results in the accumulation of VASP at cell-cell adhesions and a concomitant increase in cell-cell adhesion.
authors.affiliation: Physiology and Developmental Biology, Brigham Young University, 574 WIDB, Provo, UT 84602, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Thomson
authors.forename: Marc P A
authors.initials: MP
authors.lastname: Ascione
authors.forename: Jacob
authors.initials: J
authors.lastname: Grange
authors.forename: Cody
authors.initials: C
authors.lastname: Nelson
authors.forename: Marc D H
authors.initials: MD
authors.lastname: Hansen
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004285:Dogs; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D012694:Serine / Q000235:genetics / Q000378:metabolism*; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D000199:Actins; D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D010750:Phosphoproteins; D000098662:Vasodilator-Stimulated Phosphoprotein; D012694:Serine; D055372:AMP-Activated Protein Kinases