The carboxy-terminal domain of Grp94 binds to protein kinase CK2α but not to CK2 holoenzyme

Surface plasmon resonance analysis shows that the carboxy-terminal domain of Grp94 (Grp94-CT, residues 518–803) physically interacts with the catalytic subunit of protein kinase CK2 (CK2α) under non-stressed conditions. A K D of 4×10 −7 was determined for this binding. Heparin competed with Grp94-CT for binding to CK2α. CK2β also inhibited the binding of Grp94-CT to CK2α, and CK2 holoenzyme reconstituted in vitro was unable to bind Grp94-CT. The use of CK2α mutants made it possible to map the Grp94-CT binding site to the four lysine stretch (residues 74–77) present in helix C of CK2α. Grp94-CT stimulated the activity of CK2α wild-type but was ineffective on the CK2α K74–77A mutant.