ArticleThe Journal of biological chemistry2014
Requirements for pseudosubstrate arginine residues during autoinhibition and phosphatidylinositol 3,4,5-(PO₄)₃-dependent activation of atypical PKC.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- GCL pruning of PIP3 establishes the soma-germline boundary.The Journal of cell biology · 2026Article
- Into the fold: advances in understanding aPKC membrane dynamics.The Biochemical journal · 2023Article
- Cooperative regulation of C1-domain membrane recruitment polarizes atypical protein kinase C.The Journal of cell biology · 2023Article
- Control of atypical PKCι membrane dissociation by tyrosine phosphorylation within a PB1-C1 interdomain interface.The Journal of biological chemistry · 2023Article
- Role of ceramides in diabetic foot ulcers (Review).International journal of molecular medicine · 2023Review
- Impact of peptide permeation enhancer on tight junctions opening cellular mechanisms.Biochemistry and biophysics reports · 2022Article
- The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Review
- Review
- Identification of Key Phospholipids That Bind and Activate Atypical PKCs.Biomedicines · 2021Article
- aPKC: the Kinase that Phosphorylates Cell Polarity.F1000Research · 2018Review
- Cell Polarity in Cerebral Cortex Development-Cellular Architecture Shaped by Biochemical Networks.Frontiers in cellular neuroscience · 2017Review
- Pleckstrin Homology (PH) Domain Leucine-rich Repeat Protein Phosphatase Controls Cell Polarity by Negatively Regulating the Activity of Atypical Protein Kinase C.The Journal of biological chemistry · 2016Article
- PIP3-binding proteins promote age-dependent protein aggregation and limit survival in C. elegans.Oncotarget · 2016Article
- Molecular Control of Atypical Protein Kinase C: Tipping the Balance between Self-Renewal and Differentiation.Journal of molecular biology · 2016Review
- Protein kinase Cζ exhibits constitutive phosphorylation and phosphatidylinositol-3,4,5-triphosphate-independent regulation.The Biochemical journal · 2016Article
- BMI-related progression of atypical PKC-dependent aberrations in insulin signaling through IRS-1, Akt, FoxO1 and PGC-1α in livers of obese and type 2 diabetic humans.Metabolism: clinical and experimental · 2015Article
- Protein Kinase C (PKC)ζ Pseudosubstrate Inhibitor Peptide Promiscuously Binds PKC Family Isoforms and Disrupts Conventional PKC Targeting and Translocation.Molecular pharmacology · 2015Article
- Modulation of Insulin Sensitivity of Hepatocytes by the Pharmacological Downregulation of Phospholipase D.International journal of endocrinology · 2015Article
- Hepatic Atypical Protein Kinase C: An Inherited Survival-Longevity Gene that Now Fuels Insulin-Resistant Syndromes of Obesity, the Metabolic Syndrome and Type 2 Diabetes Mellitus.Journal of clinical medicine · 2014Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Atypical PKC (aPKC) isoforms are activated by the phosphatidylinositol 3-kinase product phosphatidylinositol 3,4,5-(PO4)3 (PIP3). How PIP3 activates aPKC is unknown. Although Akt activation involves PIP3 binding to basic residues in the Akt pleckstrin homology domain, aPKCs lack this domain. Here we examined the role of basic arginine residues common to aPKC pseudosubstrate sequences. Replacement of all five (or certain) arginine residues in the pseudosubstrate sequence of PKC-ι by site-directed mutagenesis led to constitutive activation and unresponsiveness to PIP3 in vitro or insulin in vivo. However, with the addition of the exogenous arginine-containing pseudosubstrate tridecapeptide to inhibit this constitutively active PKC-ι, PIP3-activating effects were restored. A similar restoration of responsiveness to PIP3 was seen when exogenous pseudosubstrate was used to inhibit mouse liver PKC-λ/ζ maximally activated by insulin or ceramide and a truncated, constitutively active PKC-ζ mutant lacking all regulatory domain elements and containing "activating" glutamate residues at loop and autophosphorylation sites (Δ1-247/T410E/T560E-PKC-ζ). NMR studies suggest that PIP3 binds directly to the pseudosubstrate. The ability of PIP3 to counteract the inhibitory effects of the exogenous pseudosubstrate suggests that basic residues in the pseudosubstrate sequence are required for maintaining aPKCs in an inactive state and are targeted by PIP3 for displacement from the substrate-binding site during kinase activation.
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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.