The mitotic serine/threonine kinase Aurora2/AIK is regulated by phosphorylation and degradation.
Aurora2 is a cell cycle regulated serine/threonine protein kinase which is overexpressed in many tumor cell lines. We demonstrate that Aurora2 is regulated by phosphorylation in a cell cycle dependent manner. This phosphorylation occurs on a conserved residue, Threonine 288, within the activation loop of the catalytic domain of the kinase and results in a significant increase in the enzymatic activity. Threonine 288 resides within a consensus motif for the cAMP dependent kinase and can be phosphorylated by PKA in vitro. The protein phosphatase 1 is shown to dephosphorylate this site in vitro, and in vivo the phosphorylation of T288 is induced by okadaic acid treatment. Furthermore, we show that the Aurora2 kinase is regulated by proteasome dependent degradation and that Aurora2 phosphorylated on T288 may be targeted for degradation during mitosis. Our experiments suggest that phosphorylation of T288 is important for regulation of the Aurora2 kinase both for its activity and its stability.
Walter
A O
AO
DNAX Research Institute, Palo Alto, California 94304, USA.
Seghezzi
W
W
Korver
W
W
Sheung
J
J
Lees
E
E
D000595:Amino Acid Sequence; D064127:Aurora Kinases; D020134:Catalytic Domain; D002453:Cell Cycle; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006367:HeLa Cells / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D008938:Mitosis; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D009363:Neoplasm Proteins / Q000378:metabolism; D019319:Okadaic Acid / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010769:Phosphothreonine / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D054645:Protein Phosphatase 1; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014452:Ubiquitins / Q000378:metabolism
D009097:Multienzyme Complexes; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; D014452:Ubiquitins; D010769:Phosphothreonine; D019319:Okadaic Acid; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex