The phosphorylation of CDK at Thr-160 by CAK leads to:
CDK activation involves multiple ordered modifications ensuring integration of multiple regulatory inputs. Monomeric CDK presents T-loop obstructing peptide substrate binding and PSTAIRE helix oriented outward preventing coordination of ATP phosphates. Cyclin association through extensive hydrophobic interface rotates PSTAIRE helix inward aligning Glu51 with Lys33 for ATP positioning and partially displaces T-loop. However maximal substrate affinity requires phosphorylation of conserved threonine within T-loop, Thr160 in CDK2, Thr161 in CDK1, Thr172 in CDK4, catalyzed by CDK-activating kinase
Ref: Fisher & Morgan, CAK Phosphorylation of CDK at Thr160 and Activation Mechanism, Cell 1994; Alberts et al., Chapter 17, CDK Activation Steps.
