CDK1 phosphorylation state

A CDK1 phosphorylation state identifies modified amino acid residues. Different sites have opposite effects: in studied Xenopus laevis Cdc2, Thr14/Tyr15 are inhibitory, while Thr161 phosphorylation is activating. T denotes a threonine residue, Y a tyrosine residue, and numbers are protein primary structure positions. Do not assume this numbering for every species.^[ref]

The 1992 study supplies a useful separation of mechanisms: replacing Thr14, Tyr15 and Thr161 still permitted cyclin B binding, but replacing Thr161 prevented activation of histone H1 phosphorylation. Binding therefore did not suffice for catalytic activity in that preparation. Activating phosphorylation also occurred with catalytically inactive Cdc2, supporting a separate CDK-activating kinase rather than a requirement for intramolecular autophosphorylation.^[ref]

In this deliberately coarse classification, bound cyclin B, activating phosphorylation, and cleared inhibitory sites must coincide for the activity-permissive state. Removing inhibitory phosphate groups does not supply missing cyclin B or activating phosphorylation. Conversely, adding activating phosphorylation does not erase inhibitory modification. Actual preparations contain mixtures of states and additional regulators; this classification gives no numerical reaction rate.

A CDK-activating kinase is a protein kinase supplying activating phosphorylation to a cyclin-dependent kinase 1 preparation. The Xenopus laevis experiment above distinguished this activity from the catalytic activity of Cdc2 itself. CAK names that function here, without asserting that every species uses the same protein assembly.

Myt1 is a protein kinase distinct from Wee1. The cloned Xenopus laevis Myt1 phosphorylated Cdc2 at both inhibitory sites Thr14 and Tyr15; depletion experiments implicated it as the predominant Thr14-directed activity in Xenopus laevis egg extracts.^[ref]