Phosphorylation of annexin I by TRPM7 channel-kinase.
TRPM7 is an unusual bifunctional molecule consisting of a TRP ion channel fused to a protein kinase domain. It has been shown that TRPM7 plays a key role in the regulation of intracellular magnesium homeostasis as well as in anoxic neuronal death. TRPM7 channel has been characterized using electrophysiological techniques; however, the function of the kinase domain is not known and endogenous substrates for the kinase have not been reported previously. Here we have identified annexin 1 as a substrate for TRPM7 kinase. Phosphorylation of annexin 1 by TRPM7 kinase is stimulated by Ca2+ and is dramatically increased in extracts from cells overexpressing TRPM7. Phosphorylation of annexin 1 by TRPM7 kinase occurs at a conserved serine residue (Ser5) located within the N-terminal amphipathic alpha-helix of annexin 1. The N-terminal region plays a crucial role in interaction of annexin 1 with other proteins and membranes, and therefore, phosphorylation of annexin 1 at Ser5 by TRPM7 kinase may modulate function of annexin 1.
Dorovkov
Maxim V
MV
Department of Pharmacology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
Ryazanov
Alexey G
AG
D000595:Amino Acid Sequence; D000818:Animals; D017305:Annexin A1 / Q000737:chemistry*; D001665:Binding Sites; D002118:Calcium / Q000737:chemistry; D002402:Cathepsin D / Q000494:pharmacology; D002460:Cell Line; D015180:Electrophoresis, Gel, Two-Dimensional; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007473:Ion Channels / Q000378:metabolism / Q000502:physiology*; D007477:Ions; D008274:Magnesium / Q000737:chemistry; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010455:Peptides / Q000737:chemistry; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism / Q000502:physiology*; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D012694:Serine / Q000737:chemistry; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D050053:TRPM Cation Channels; D014357:Trypsin / Q000494:pharmacology
D017305:Annexin A1; D007473:Ion Channels; D007477:Ions; D008565:Membrane Proteins; D010455:Peptides; D011994:Recombinant Proteins; D050053:TRPM Cation Channels; D012694:Serine; D011494:Protein Kinases; C421903:Trpm7 protein, mouse; D014357:Trypsin; D002402:Cathepsin D; D008274:Magnesium; D002118:Calcium