A calmodulin-regulated kinase (CaM-kinase) is involved in spatial learning and memory. This kinase is able to phosphorylate itself such that its kinase activity is now independent of the intracellular concentration of Ca2+

Question

Thus, the kinase stays active after Ca2+ levels have dropped. Mice completely lacking this CaM-kinase have severe spatial learning defects but are otherwise normal.
A. Each of the following mutations also leads to similar learning defects. For each case explain why.
(1) a mutation that prevents the kinase from binding ATP
(2) a mutation that deletes the calmodulin-binding part of the kinase
(3) a mutation that destroys the site of autophosphorylation
B. What would be the effect on the activity of CaM-kinase if there were a mutation that reduced its interaction with the protein phosphatase responsible for inactivating the kinase?

Answer 1

A. Because a complete lack of the CaM-kinase causes a learning defect, we can assume that mutations leading to inactivation of the kinase would also have a similar effect.
(1) Protein kinases have a binding site for ATP, which is the source of the phosphate used for phosphorylating their target proteins; if the kinase cannot bind ATP, it will be inactive.
(2)Because binding to calmodulin in the presence of Ca2+ activates CaM-kinases, deletion of the calmodulin-binding portion would inactivate the kinase.
(3)A mutation that destroys the site of autophosphorylation will also impair the normal function of the kinase, because the kinase will become inactive as soon as Ca2+ levels decrease.
B. The kinase would stay active for longer after a transient increase in intracellular Ca2+ concentration.