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.
Department of Pharmacology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
Maxim V
MV
Dorovkov
Alexey G
AG
Ryazanov
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