ArticleMolecular cell2019
Protein Kinase C Quality Control by Phosphatase PHLPP1 Unveils Loss-of-Function Mechanism in Cancer.
Article in Molecular cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
39 citing papers in PubMed, 59 citations in OpenAlex.
- A chemigenetic endogenous Ras activity biosensor for live-cell pharmacology.Nature chemical biology · 2026Article
- PHLPP is neither a Phosphatase nor a Tumor Suppressor.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- Sex-specific disruptions in PKCγ signaling in a mouse model of spinocerebellar ataxia type 14.JCI insight · 2026Article
- Molecular basis of allosteric regulation and pharmaceutical targeting of protein kinase Cβ.Nature communications · 2026Article
- Protein kinase C theta: evolution, regulation, and function.The Biochemical journal · 2026Review
- Penetrant PKCβ mutation in ATLL displays a mixed gain-of-function.The Biochemical journal · 2025Article
- Comprehensive computational analysis of PKCδ non-synonymous variants identifies rs1703863535 as a potential breast cancer biomarker.BMC cancer · 2025Article
- Phlpp1 alters the murine chondrocyte phospho-proteome during endochondral bone formation.Bone · 2024Article
- Cancer-associated mutations in protein kinase C theta are loss-of-function.The Biochemical journal · 2024Article
- Article
- Single-residue mutation in protein kinase C toggles between cancer and neurodegeneration.The Biochemical journal · 2023Article
- Protein Kinase C at the Crossroad of Mutations, Cancer, Targeted Therapy and Immune Response.Biology · 2023Review
- Non-synonymous SNPs variants of PRKCG and its association with oncogenes predispose to hepatocellular carcinoma.Cancer cell international · 2023Article
- Multi-omics profiling of papillary thyroid microcarcinoma reveals different somatic mutations and a unique transcriptomic signature.Journal of translational medicine · 2023Article
- FKBP51 plays an essential role in Akt ubiquitination that requires Hsp90 and PHLPP.Cell death & disease · 2023Article
- Darovasertib, a novel treatment for metastatic uveal melanoma.Frontiers in pharmacology · 2023Review
- Emerging roles of PHLPP phosphatases in lung cancer.Frontiers in oncology · 2023Review
- Enhanced activity of Alzheimer disease-associated variant of protein kinase Cα drives cognitive decline in a mouse model.Nature communications · 2022Article
- Protein Kinase C (PKC) Isozymes as Diagnostic and Prognostic Biomarkers and Therapeutic Targets for Cancer.Cancers · 2022Review
- PHLPP1 regulates CFTR activity and lumen expansion through AMPK.Development (Cambridge, England) · 2022Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Protein kinase C (PKC) isozymes function as tumor suppressors in increasing contexts. In contrast to oncogenic kinases, whose function is acutely regulated by transient phosphorylation, PKC is constitutively phosphorylated following biosynthesis to yield a stable, autoinhibited enzyme that is reversibly activated by second messengers. Here, we report that the phosphatase PHLPP1 opposes PKC phosphorylation during maturation, leading to the degradation of aberrantly active species that do not become autoinhibited. Cancer-associated hotspot mutations in the pseudosubstrate of PKCβ that impair autoinhibition result in dephosphorylated and unstable enzymes. Protein-level analysis reveals that PKCα is fully phosphorylated at the PHLPP site in over 5,000 patient tumors, with higher PKC levels correlating (1) inversely with PHLPP1 levels and (2) positively with improved survival in pancreatic adenocarcinoma. Thus, PHLPP1 provides a proofreading step that maintains the fidelity of PKC autoinhibition and reveals a prominent loss-of-function mechanism in cancer by suppressing the steady-state levels of PKC.
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Registered trials
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.