Characterization of peptide interactions that regulate PKCÎµ activation
Targeting the interaction between PKC isoforms and their anchoring proteins can specifically regulate kinase activity. epsilonV1-2 and pseudoepsilonRACK peptides, derived from the PKCepsilon C2 domain, modulate its association with receptor for activated C-kinase 2 (RACK2) and thus its function. Details of these interactions remain obscure, and we therefore investigated binding of these peptides using biophysical techniques. Surface plasmon resonance (SPR) indicated that the inhibitory epsilonV1-2 peptide bound to RACK2, and inhibited PKCepsilon binding as expected. In contrast, SPR and NMR demonstrated that the activating pseudoepsilonRACK peptide and related sequences did not bind to PKCepsilon, indicating that their mechanisms of action do not involve binding to the kinase as previously proposed. Our results clarify which interactions could be targeted in developing new therapeutics that inhibit PKCepsilon-RACK2 interaction.
|Authors||Chandrashekaran, I. R., Norton, R. S., Schmitz-Peiffer, C.|
|Responsible Garvan Author|
|Publisher Name||FEBS LETTERS|
|Published Date||2017-12-20 00:00:00|
|URL link to publisher's version||https://www.ncbi.nlm.nih.gov/pubmed/29266266|