title: Aurora A kinase activity influences calcium signaling in kidney cells.
abstract: Most studies of Aurora A (AurA) describe it as a mitotic centrosomal kinase. However, we and others have recently identified AurA functions as diverse as control of ciliary resorption, cell differentiation, and cell polarity control in interphase cells. In these activities, AurA is transiently activated by noncanonical signals, including Ca(2+)-dependent calmodulin binding. These and other observations suggested that AurA might be involved in pathological conditions, such as polycystic kidney disease (PKD). In this paper, we show that AurA is abundant in normal kidney tissue but is also abnormally expressed and activated in cells lining PKD-associated renal cysts. PKD arises from mutations in the PKD1 or PKD2 genes, encoding polycystins 1 and 2 (PC1 and PC2). AurA binds, phosphorylates, and reduces the activity of PC2, a Ca(2+)-permeable nonselective cation channel and, thus, limits the amplitude of Ca(2+) release from the endoplasmic reticulum. These and other findings suggest AurA may be a relevant new biomarker or target in the therapy of PKD.
authors.affiliation: Department of Developmental Therapeutics, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Plotnikova
authors.forename: Elena N
authors.initials: EN
authors.lastname: Pugacheva
authors.forename: Erica A
authors.initials: EA
authors.lastname: Golemis
mesh_terms: D000818:Animals; D064096:Aurora Kinase A; D064127:Aurora Kinases; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D007690:Polycystic Kidney Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D050396:TRPP Cation Channels / Q000235:genetics / Q000378:metabolism
chemical_list: D064096:Aurora Kinase A; D064127:Aurora Kinases; D002118:Calcium; D017346:Protein Serine-Threonine Kinases; D050396:TRPP Cation Channels; C576918:Aurka protein, mouse