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The Kinase Specificity of Protein Kinase Inhibitor Peptide

G-protein-coupled-receptor (GPCR) signaling is exquisitely controlled to achieve spatial and temporal specificity. The endogenous protein kinase inhibitor peptide (PKI) confines the spatial and temporal spread of the activity of protein kinase A (PKA), which integrates inputs from three major types...

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Detalles Bibliográficos
Autores principales: Chen, Yao, Sabatini, Bernardo L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878667/
https://www.ncbi.nlm.nih.gov/pubmed/33584320
http://dx.doi.org/10.3389/fphar.2021.632815
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author Chen, Yao
Sabatini, Bernardo L.
author_facet Chen, Yao
Sabatini, Bernardo L.
author_sort Chen, Yao
collection PubMed
description G-protein-coupled-receptor (GPCR) signaling is exquisitely controlled to achieve spatial and temporal specificity. The endogenous protein kinase inhibitor peptide (PKI) confines the spatial and temporal spread of the activity of protein kinase A (PKA), which integrates inputs from three major types of GPCRs. Despite its wide usage as a pharmaceutical inhibitor of PKA, it was unclear whether PKI only inhibits PKA activity. Here, the effects of PKI on 55 mouse kinases were tested in in vitro assays. We found that in addition to inhibiting PKA activity, both PKI (6–22) amide and full-length PKIα facilitated the activation of multiple isoforms of protein kinase C (PKC), albeit at much higher concentrations than necessary to inhibit PKA. Thus, our results call for appropriate interpretation of experimental results using PKI as a pharmaceutical agent. Furthermore, our study lays the foundation to explore the potential functions of PKI in regulating PKC activity and in coordinating PKC and PKA activities.
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spelling pubmed-78786672021-02-13 The Kinase Specificity of Protein Kinase Inhibitor Peptide Chen, Yao Sabatini, Bernardo L. Front Pharmacol Pharmacology G-protein-coupled-receptor (GPCR) signaling is exquisitely controlled to achieve spatial and temporal specificity. The endogenous protein kinase inhibitor peptide (PKI) confines the spatial and temporal spread of the activity of protein kinase A (PKA), which integrates inputs from three major types of GPCRs. Despite its wide usage as a pharmaceutical inhibitor of PKA, it was unclear whether PKI only inhibits PKA activity. Here, the effects of PKI on 55 mouse kinases were tested in in vitro assays. We found that in addition to inhibiting PKA activity, both PKI (6–22) amide and full-length PKIα facilitated the activation of multiple isoforms of protein kinase C (PKC), albeit at much higher concentrations than necessary to inhibit PKA. Thus, our results call for appropriate interpretation of experimental results using PKI as a pharmaceutical agent. Furthermore, our study lays the foundation to explore the potential functions of PKI in regulating PKC activity and in coordinating PKC and PKA activities. Frontiers Media S.A. 2021-01-29 /pmc/articles/PMC7878667/ /pubmed/33584320 http://dx.doi.org/10.3389/fphar.2021.632815 Text en Copyright © 2021 Chen and Sabatini. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Chen, Yao
Sabatini, Bernardo L.
The Kinase Specificity of Protein Kinase Inhibitor Peptide
title The Kinase Specificity of Protein Kinase Inhibitor Peptide
title_full The Kinase Specificity of Protein Kinase Inhibitor Peptide
title_fullStr The Kinase Specificity of Protein Kinase Inhibitor Peptide
title_full_unstemmed The Kinase Specificity of Protein Kinase Inhibitor Peptide
title_short The Kinase Specificity of Protein Kinase Inhibitor Peptide
title_sort kinase specificity of protein kinase inhibitor peptide
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878667/
https://www.ncbi.nlm.nih.gov/pubmed/33584320
http://dx.doi.org/10.3389/fphar.2021.632815
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