Characterization of a novel cdk1-related kinase.
The p13suc1/p9CKShs proteins bind tightly to the cyclin-dependent kinases cdk1 and cdk2. The distantly related protein, p15cdk-BP, binds cdk4/6, cdk5 and cdk8. We now show that immobilized p15cdk-BP binds both an HMG-I kinase and a 35-kDa protein that cross-reacts with anti-PSTAIRE antibodies (PSTAIRE is a totally conserved motif located in subdomain III of cdk). This 'cdkX' and the HMG-I kinase also bind to an immobilized inhibitor of cdks (HD). Several properties clearly distinguish cdkX, and its associated HMG-I kinase, from known anti-PSTAIRE cross-reactive cdks: (a) cdkX migrates, in SDS/PAGE, in a position intermediate between prophase phosphorylated cdk1 and metaphase dephosphorylated cdk1; (b) in contrast with cdk1, cdkX and associated HMG-I kinase activity do not decrease following successive depletions on p9CKShs1-sepharose; (c) cdkX and associated HMG-I kinase activity, but not cdk1, decrease following depletions on immobilized inhibitor; (d) cdkX is expressed during the early development of sea urchin embryos; in contrast with cdk1/cyclin B kinase, the p15cdk-BP-bound HMG-I kinase is active throughout the cell cycle; compared with cdk1 it is active later in development; (e) p15cdk-BP-bound HMG-I kinase is essentially insensitive to powerful inhibitors of cdk such as purvalanol, roscovitine, olomoucine, p21cip1 and p16INK4A; HD is only moderately inhibitory. Altogether these results suggest the existence of a new cdk1-related kinase, possibly involved in the regulation of early development. The presence of this kinase in all organisms investigated so far, from plants to mammals, calls for its definitive identification.
Détivaud
L
L
CNRS, Station Biologique, Roscoff, France.
Pettit
G R
GR
Meijer
L
L
D000818:Animals; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D047108:Embryonic Development; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D009865:Oocytes / Q000166:cytology / Q000201:enzymology; D011418:Prophase; D011485:Protein Binding; D012617:Sea Urchins / Q000196:embryology / Q000201:enzymology; D013215:Starfish / Q000196:embryology / Q000201:enzymology; D014981:Xenopus
D004791:Enzyme Inhibitors; D018844:Cyclin-Dependent Kinases