Cdc2-cyclin B phosphorylates p70 S6 kinase on Ser411 at mitosis.
The carboxyl terminus of p70 S6 kinase (p70(s6k)) has a set of Ser and Thr residues (Ser411, Ser418, Ser424, and Thr421) phosphorylated in vivo by an unidentified kinase(s). These Ser/Thr sites are immediately followed by proline, a motif that is commonly seen in the substrates of cyclin-dependent kinases (Cdk) and mitogen-activated protein kinases. A previous study has shown that Cdc2 (Cdk1) indeed phosphorylates these p70(s6k) Ser/Thr residues in vitro. Here, we demonstrate that Cdc2-cyclin B complex phosphorylates Ser411 in the KIRSPRR sequence, whereas other Cdk-cyclin complexes including those containing Cdk2, Cdk4, or Cdk6 do not. Additionally, Ser411 phosphorylation in vivo was increased at mitosis in parallel with Cdc2 activation, and it was suppressed by a dominant negative form of Cdc2. These data indicate that p70(s6k) is a physiological substrate of Cdc2-cyclin B in mitosis. Since the activity of p70(s6k) is low during mitosis, Cdc2-cyclin B may play a role in inactivating p70(s6k) during mitosis, where protein synthesis is suppressed.
Papst
P J
PJ
Division of Basic Sciences, Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
Sugiyama
H
H
Nagasawa
M
M
Lucas
J J
JJ
Maller
J L
JL
Terada
N
N
D000595:Amino Acid Sequence; D000818:Animals; D016203:CDC2 Protein Kinase / Q000502:physiology*; D002478:Cells, Cultured; D019926:Cyclin B / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008938:Mitosis / Q000502:physiology; D008969:Molecular Sequence Data; D015739:Nocodazole / Q000494:pharmacology; D010748:Phosphopeptides / Q000378:metabolism; D010766:Phosphorylation; D010768:Phosphoserine / Q000032:analysis; D011994:Recombinant Proteins / Q000378:metabolism; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D014162:Transfection / Q000235:genetics
D019926:Cyclin B; D010748:Phosphopeptides; D011994:Recombinant Proteins; D010768:Phosphoserine; D012694:Serine; D019893:Ribosomal Protein S6 Kinases; D016203:CDC2 Protein Kinase; D015739:Nocodazole