Phosphorylation of TPX2 by Plx1 enhances activation of Aurora A.
Entry into mitosis requires the activation of mitotic kinases, including Aurora A and Polo-like kinase 1 (Plk1). Increased levels of these kinases are frequently found associated with human cancers, and therefore it is imperative to understand the processes leading to their activation. We demonstrate that TPX2, but neither Ajuba nor Inhibitor-2, can activate Aurora A directly. Moreover, Plx1 can induce Aurora A T-loop phosphorylation indirectly in vivo during oocyte maturation. We identify Ser204 in TPX2 as a Plx1 phosphorylation site. Mutating Ser204 to alanine decreases activation of Aurora A, whereas a phosphomimetic Asp mutant exhibits enhanced activating ability. Finally, we show that phosphorylation of TPX2 with Plx1 increases its ability to activate Aurora A. Taken together, our data indicate that Plx1 promotes activation of Aurora A, most likely through TPX2. In light of the current literature, we propose a model in which Plx1 and Aurora A activate each other in a positive feedback loop.
Eckerdt
Frank
F
Howard Hughes Medical Institute and Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Pascreau
Gaetan
G
Phistry
Meridee
M
Lewellyn
Andrea L
AL
DePaoli-Roach
Anna A
AA
Maller
James L
JL
D000818:Animals; D064127:Aurora Kinases; D016466:CHO Cells / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D018398:Homeodomain Proteins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D029867:Xenopus Proteins / Q000378:metabolism*; D014982:Xenopus laevis / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
D064127:Aurora Kinases; D018797:Cell Cycle Proteins; D018398:Homeodomain Proteins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D029867:Xenopus Proteins; C486551:TPX2 protein, Xenopus; C101085:Plk1 protein, Xenopus; D000097869:Polo-Like Kinase 1