Question

You may choose more than one answer. Activation of protein kinase C (PKC) involves:

DAG associates with the membrane and allosterically binds PKC

Calcium decreases the affinity of PKC for negatively charged lipids

Regulated by phosphorylation at specfic sites

Removal of psuedosubstrate from kinase core

C2 domain binding of phosphatidylserine (to be membrane attached)

Answer 1

PKC gets activated by increased amount of DAG and Ca²⁺, phosphorylation and phosphatidylserine.

PKC have C1 domain, the binding site of DAG and C2 domain, the binding site for Ca²⁺. When the concentration of both Ca²⁺ and DAG increase more than threshold, they bind to C2 and C1 domain respectively and allow PKC to interect with membrane. This interaction of PKC to membrane releases the psuedosubstrate from the active site of PKC and it get activated.

Psuedosubstrate is a small amino acid sequence which lack negatively charged amino acid serine, threonine and get attached to the active site of PKC and inactivate it.

On Ca²⁺ binding, this substrate releases the PKC's active site and thus decreases the affinity of it for negatively charges lipids, as positively charged substrate is released.

For allosteric binding of PKC to membrane, proper folding is required which is done by phosphorylation at specific site, i.e., on activation loop.