Question

Describe in detail how the entire PKC pathway works, and diagram.  Since we know the PKC pathway is activated by certain polypeptide hormones.

Answer 1

Protein kinase C, known as  PKC (EC 2.7.11.13), is a family of protein kinase enzymes that   control the function of other proteins through the phosphorylation of hydroxyl groups of serine and threonine amino acid residues on these proteins. PKC enzymes in turn are activated by increase in the concentration of diacylglycerol (DAG) or calcium ions (Ca²⁺).^[1] Hence PKC enzymes play important roles in several signal transduction cascades.^[2]

The PKC family consists of fifteen isozymes in humans.^[3] They are divided into three subfamilies, based on their second messenger requirements: conventional (or classical), novel, and atypical.^[4] Conventional (c)PKCs require Ca²⁺, DAG, and a phospholipid such as phosphatidylserine for activation. Novel (n)PKCs include require DAG, but do not require Ca²⁺ for activation. Thus, conventional and novel PKCs are activated through the same signal transduction pathway as phospholipase C. On the other hand, atypical (a)PKCs require neither Ca²⁺ nor diacylglycerol for activation. The term "protein kinase C" usually refers to the entire family of isoforms.

The structure of all PKCs consists of a regulatory domain and a catalytic domain chained  together by a hinge region. The catalytic region is highly conserved among the different isoforms, as well as, to a lesser degree, among the catalytic region of other serine/threonine kinases. The second messenger requirement differences in the isoforms are a result of the regulatory region, which are similar within the classes, but differ among them. Most of the crystal structure of the catalytic region of PKC has not been determined, except for PKC theta and iota. Due to its similarity to other kinases whose crystal structure have been determined, the structure can be strongly predicted.

Pathway Diagram: