title: Calcium is the switch in the moonlighting dual function of the ligand-activated receptor kinase phytosulfokine receptor 1.
abstract: BACKGROUND
  A number of receptor kinases contain guanylate cyclase (GC) catalytic centres encapsulated in the cytosolic kinase domain. A prototypical example is the phytosulfokine receptor 1 (PSKR1) that is involved in regulating growth responses in plants. PSKR1 contains both kinase and GC activities however the underlying mechanisms regulating the dual functions have remained elusive.
  
  
  RESULTS
  Here, we confirm the dual activity of the cytoplasmic domain of the PSKR1 receptor. We show that mutations within the guanylate cyclase centre modulate the GC activity while not affecting the kinase catalytic activity. Using physiologically relevant Ca2+ levels, we demonstrate that its GC activity is enhanced over two-fold by Ca2+ in a concentration-dependent manner. Conversely, increasing Ca2+ levels inhibits kinase activity up to 500-fold at 100 nM Ca2+.
  
  
  CONCLUSIONS
  Changes in calcium at physiological levels can regulate the kinase and GC activities of PSKR1. We therefore propose a functional model of how calcium acts as a bimodal switch between kinase and GC activity in PSKR1 that could be relevant to other members of this novel class of ligand-activated receptor kinases.
authors.forename: Victor
authors.initials: V
authors.lastname: Muleya
authors.forename: Janet I
authors.initials: JI
authors.lastname: Wheeler
authors.forename: Oziniel
authors.initials: O
authors.lastname: Ruzvidzo
authors.forename: Lubna
authors.initials: L
authors.lastname: Freihat
authors.forename: David T
authors.initials: DT
authors.lastname: Manallack
authors.forename: Chris
authors.initials: C
authors.lastname: Gehring
authors.forename: Helen R
authors.initials: HR
authors.lastname: Irving
mesh_terms: D029681:Arabidopsis Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002384:Catalysis; D006162:Guanylate Cyclase / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D008958:Models, Molecular; D009154:Mutation; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D029681:Arabidopsis Proteins; D008024:Ligands; C515018:PSKR1 protein, Arabidopsis; D011956:Receptors, Cell Surface; D006162:Guanylate Cyclase; D002118:Calcium