Question

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+. 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

Mutations that prevent the kinase from binding ATP, delete the calmodulin-binding part of the kinase, or destroy the site of autophosphorylation lead to similar learning defects in mice lacking the CaM-kinase. A mutation that reduces the interaction with the protein phosphatase responsible for inactivating the kinase would increase the activity of the CaM-kinase.

Step-by-step explanation:

Answer:

(1) A mutation that prevents the kinase from binding ATP will lead to similar learning defects because ATP is required for the kinase to phosphorylate its target substrates. Without ATP binding, the kinase cannot carry out its function and the spatial learning process will be impaired.
(2) A mutation that deletes the calmodulin-binding part of the kinase will also result in learning defects. Calmodulin is an essential regulator of the kinase and its binding is necessary for the activation of the kinase. Without the ability to bind calmodulin, the kinase will not be able to function properly.
(3) A mutation that destroys the site of autophosphorylation will lead to similar learning defects as autophosphorylation is an important mechanism for the kinase to activate itself. Without autophosphorylation, the kinase will not be able to maintain its activity independent of the intracellular concentration of Ca2+, leading to impaired spatial learning and memory.

Bonus question:

If there were a mutation that reduced the interaction between the CaM-kinase and the protein phosphatase responsible for inactivating the kinase, it would result in increased activity of the CaM-kinase. Protein phosphatases are responsible for dephosphorylating the kinase and inactivating it. If the interaction between the kinase and the phosphatase is reduced, the kinase would remain active for a longer period of time, leading to enhanced phosphorylation and potentially dysregulated cellular processes.