ArticleThe Journal of biological chemistry2015
Zeta Inhibitory Peptide Disrupts Electrostatic Interactions That Maintain Atypical Protein Kinase C in Its Active Conformation on the Scaffold p62.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 35 citations in OpenAlex.
- aPKC-ζ III promotes trophoblast fusion by altering Par-3 interactions with Hippo signaling kinase LATS1.Stem cell reports · 2026Article
- Rosmarinic acid-mediated downregulation of RIG-I and p62 in microglia confers resistance to Japanese encephalitis virus-induced inflammation.BMC veterinary research · 2024Article
- A Multimodel Study of the Role of Novel PKC Isoforms in the DNA Integrity Checkpoint.International journal of molecular sciences · 2023Article
- Cooperative regulation of C1-domain membrane recruitment polarizes atypical protein kinase C.The Journal of cell biology · 2023Article
- Loss of polarity regulators initiates gasdermin-E-mediated pyroptosis in syncytiotrophoblasts.Life science alliance · 2023Article
- Storming the gate: New approaches for targeting the dynamic tight junction for improved drug delivery.Advanced drug delivery reviews · 2023Review
- Structure-activity relationship of a peptide permeation enhancer.Tissue barriers · 2023Article
- Impact of peptide permeation enhancer on tight junctions opening cellular mechanisms.Biochemistry and biophysics reports · 2022Article
- A novel non‑selective atypical PKC agonist could protect neuronal cell line from Aβ‑oligomer induced toxicity by suppressing Aβ generation.Molecular medicine reports · 2022Article
- A Novel Role of PP2A Methylation in the Regulation of Tight Junction Assembly and Integrity.Frontiers in cell and developmental biology · 2022Article
- Activators and Inhibitors of Protein Kinase C (PKC): Their Applications in Clinical Trials.Pharmaceutics · 2021Review
- Role of Protein Kinase C in Immune Cell Activation and Its Implication Chemical-Induced Immunotoxicity.Advances in experimental medicine and biology · 2021Article
- Reversing Cocaine-Induced Plasticity with Zeta Inhibitory Peptide.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- aPKC in neuronal differentiation, maturation and function.Neuronal signaling · 2019Review
- Experiments with Snails Add to Our Knowledge about the Role of aPKC Subfamily Kinases in Learning.International journal of molecular sciences · 2019Article
- Activation of atypical protein kinase C by sphingosine 1-phosphate revealed by an aPKC-specific activity reporter.Science signaling · 2019Article
- Actin polymerization controls cilia-mediated signaling.The Journal of cell biology · 2018Article
- Protein kinase C: perfectly balanced.Critical reviews in biochemistry and molecular biology · 2018Review
- Protein kinase C as a tumor suppressor.Seminars in cancer biology · 2018Review
- Memory Synapses Are Defined by Distinct Molecular Complexes: A Proposal.Frontiers in synaptic neuroscience · 2018Review
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Atypical protein kinase C (aPKC) enzymes signal on protein scaffolds, yet how they are maintained in an active conformation on scaffolds is unclear. A myristoylated peptide based on the autoinhibitory pseudosubstrate fragment of the atypical PKCζ, zeta inhibitory peptide (ZIP), has been extensively used to inhibit aPKC activity; however, we have previously shown that ZIP does not inhibit the catalytic activity of aPKC isozymes in cells (Wu-Zhang, A. X., Schramm, C. L., Nabavi, S., Malinow, R., and Newton, A. C. (2012) J. Biol. Chem. 287, 12879-12885). Here we sought to identify a bona fide target of ZIP and, in so doing, unveiled a novel mechanism by which aPKCs are maintained in an active conformation on a protein scaffold. Specifically, we used protein-protein interaction network analysis, structural modeling, and protein-protein docking to predict that ZIP binds an acidic surface on the Phox and Bem1 (PB1) domain of p62, an interaction validated by peptide array analysis. Using a genetically encoded reporter for PKC activity fused to the p62 scaffold, we show that ZIP inhibits the activity of wild-type aPKC, but not a construct lacking the pseudosubstrate. These data support a model in which the pseudosubstrate of aPKCs is tethered to the acidic surface on p62, locking aPKC in an open, signaling-competent conformation. ZIP competes for binding to the acidic surface, resulting in displacement of the pseudosubstrate of aPKC and re-engagement in the substrate-binding cavity. This study not only identifies a cellular target for ZIP, but also unveils a novel mechanism by which scaffolded aPKC is maintained in an active conformation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.