title: Phosphorylation of annexin A1 by TRPM7 kinase: a switch regulating the induction of an α-helix.
abstract: TRPM7 is an unusual bifunctional protein consisting of an α-kinase domain fused to a TRP ion channel. Previously, we have identified annexin A1 as a substrate for TRPM7 kinase and found that TRPM7 phosphorylates annexin A1 at Ser5 within the N-terminal α-helix. Annexin A1 is a Ca(2+)-dependent membrane binding protein, which has been implicated in membrane trafficking and reorganization. The N-terminal tail of annexin A1 can interact with either membranes or S100A11 protein, and it adopts the conformation of an amphipathic α-helix upon these interactions. Moreover, the existing evidence indicates that the formation of an α-helix is essential for these interactions. Here we show that phosphorylation at Ser5 prevents the N-terminal peptide of annexin A1 from adopting an α-helical conformation in the presence of membrane-mimetic micelles as well as phospholipid vesicles. We also show that phosphorylation at Ser5 dramatically weakens the binding of the peptide to S100A11. Our data suggest that phosphorylation at Ser5 regulates the interaction of annexin A1 with membranes as well as S100A11 protein.
authors.affiliation: Department of Pharmacology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, New Jersey 08854, United States. dorovkma@umdnj.edu
authors.forename: Maxim V
authors.initials: MV
authors.lastname: Dorovkov
authors.forename: Alla S
authors.initials: AS
authors.lastname: Kostyukova
authors.forename: Alexey G
authors.initials: AG
authors.lastname: Ryazanov
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017305:Annexin A1 / Q000737:chemistry* / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D017433:Protein Structure, Secondary; D009418:S100 Proteins / Q000378:metabolism; D012694:Serine; D050053:TRPM Cation Channels / Q000378:metabolism*
chemical_list: D017305:Annexin A1; D010446:Peptide Fragments; D009418:S100 Proteins; D050053:TRPM Cation Channels; D012694:Serine