I could be way off base but I think I remember learning that Protein Kinase C has some effects when activated by one pathway and other effects when activated by another. How does this happen? Is it just phosphorylated differently or what?

  • $\begingroup$ Can you provide some background? Protein kinase-C would do the same job (in a molecular sense) irrespective of the upstream pathway. $\endgroup$
    Mar 7 '16 at 5:14
  • $\begingroup$ It's good to take a step back sometimes and look at a bigger picture: PKC got activated, but what else is being activated or deactivated by other signals at the same time? $\endgroup$
    – CKM
    Mar 9 '16 at 20:17

You probably remember correctly — at least in part. The part that is missing is that protein kinase C isn't just one enzyme, but perhaps a dozen different isoforms that fall into three different classes, differing, among other things in their requirements for activation (e.g. whether they require calcium ions as well as diacylglycerol). It would be theoretically possible for protein kinase C activated by one pathway to have different effects from that activated by another if the different isoforms involved had different properties. This has indeed been suggested, although it has been difficult to establish experimentally.

The following two reviews that deal with this are about 20 years old, but may allow easier general access (and are easier to read):

Dekker, L.V. and Parker, P.J. (1994) Trends in Biochemical Sciences vol 19 pp 73–77.

Jaken, S. (1996) Current Opinion in Cell Biology, vol 8, pp 168–173.

The following quotation from the summary of a more recent and more extensive review article (Steinberg, S.F. [2008] Physiol. Review. vol. 88 pp. 1341–1378) may be pertinent:

"There is growing evidence that individual PKC isoforms subserve unique (and in some cases opposing) functions in cells, at least in part as a result of isoform-specific subcellular compartmentalization patterns, protein-protein interactions, and post-translational modifications that influence catalytic function."

One other feature of protein kinase C is relevant to this question. Most other protein kinases (which tend not to have multiple isoforms) have a more or less restricted substrate specificity determined by residues of a particular type at particular positions with respect to the phosphorylation target residue (Ser, Thr or Tyr). This limits the proteins the kinases act on to specific targets. In contrast, protein kinase C can phosphorylate target residues in a wide variety of contexts. The current model (above) allows specificity of protein kinase C for target proteins to be obtained in a different way — by the specific proteins that each activated isoform binds to, i.e. by protein–protein interaction rather than target-site context.


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