Autophosphorylation Created 2026-10-13 Updated 2026-10-20
Autophosphorylation is phosphorylation of a protein kinase by its own catalytic activity or that of another member of the same protein kinase assembly. Distinguish modification within one chain from trans-autophosphorylation between partners.
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]
Figure 1.
Cyclin B binding and site-specific CDK1 phosphorylation states answer different questions
. Original qualitative schematic for the studied Xenopus laevis Cdc2. All four right-hand boxes contain bound cyclin B; only the green box has activating Thr161 phosphorylation with both inhibitory sites clear. “Inhibitory P present” groups Thr14 and/or Tyr15 modification. Arrows show changes of state, not an obligatory sequence, measured rates, or a complete cell cycle model. Myt1 can add either inhibitory modification; Cdc25 removes inhibitory phosphate groups. Details.
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.
Trans-autophosphorylation 2026-10-13
In trans-autophosphorylation, one protein kinase chain phosphorylates another partner chain. “Auto” therefore does not require the modified site and catalytic active site to be on the same chain. The insulin receptor provides an activation-loop example; EGFR shows why autophosphorylation and catalytic activation need not be the same event.