ArticleThe Journal of biological chemistry2013
Agonist-induced down-regulation of endogenous protein kinase c α through an endolysosomal mechanism.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- PKCα regulates the secretion of PDL1-carrying small extracellular vesicles in a p53-dependent manner.Cell death & disease · 2025Article
- Conventional protein kinase C in the brain: repurposing cancer drugs for neurodegenerative treatment?Neuronal signaling · 2021Review
- The complexities of PKCα signaling in cancer.Advances in biological regulation · 2021Review
- Equivocal, explicit and emergent actions of PKC isoforms in cancer.Nature reviews. Cancer · 2021Review
- Classical Protein Kinase C: a novel kinase target in breast cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2019Review
- Neurodegeneration in SCA14 is associated with increased PKCγ kinase activity, mislocalization and aggregation.Acta neuropathologica communications · 2018Article
- Characterization of AJH-836, a diacylglycerol-lactone with selectivity for novel PKC isozymes.The Journal of biological chemistry · 2018Article
- Protein kinase C mechanisms that contribute to cardiac remodelling.Clinical science (London, England : 1979) · 2016Review
- Keratin impact on PKCδ- and ASMase-mediated regulation of hepatocyte lipid raft size - implication for FasR-associated apoptosis.Journal of cell science · 2016Article
- Protein Kinase Cα (PKCα) Is Resistant to Long Term Desensitization/Down-regulation by Prolonged Diacylglycerol Stimulation.The Journal of biological chemistry · 2016Article
- Tuning the signalling output of protein kinase C.Biochemical Society transactions · 2014Review
- A kinase inhibitor screen reveals protein kinase C-dependent endocytic recycling of ErbB2 in breast cancer cells.The Journal of biological chemistry · 2014Article
- Exercise preconditioning-induced late phase of cardioprotection against exhaustive exercise: possible role of protein kinase C delta.The journal of physiological sciences : JPS · 2014Article
- Human cytomegalovirus pUL37x1-induced calcium flux activates PKCα, inducing altered cell shape and accumulation of cytoplasmic vesicles.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Heat shock proteins regulate activation-induced proteasomal degradation of the mature phosphorylated form of protein kinase C.The Journal of biological chemistry · 2013Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Protein kinase C (PKC) isozymes undergo down-regulation upon sustained stimulation. Previous studies have pointed to the existence of both proteasome-dependent and -independent pathways of PKCα processing. Here we demonstrate that these down-regulation pathways are engaged in different subcellular compartments; proteasomal degradation occurs mainly at the plasma membrane, whereas non-proteasomal processing occurs in the perinuclear region. Using cholesterol depletion, pharmacological inhibitors, RNA interference, and dominant-negative mutants, we define the mechanisms involved in perinuclear accumulation of PKCα and identify the non-proteasomal mechanism mediating its degradation. We show that intracellular accumulation of PKCα involves at least two clathrin-independent, cholesterol/lipid raft-mediated pathways that do not require ubiquitination of the protein; one is dynamin-dependent and likely involves caveolae, whereas the other is dynamin- and small GTPase-independent. Internalized PKCα traffics through endosomes and is delivered to the lysosome for degradation. Supportive evidence includes (a) detection of the enzyme in EEA1-positive early endosomes, Rab7-positive late endosomes/multivesicular bodies, and LAMP1-positive lysosomes and (b) inhibition of its down-regulation by lysosome-disrupting agents and leupeptin. Only limited dephosphorylation of PKCα occurs during trafficking, with fully mature enzyme being the main target for lysosomal degradation. These studies define a novel and widespread mechanism of desensitization of PKCα signaling that involves endocytic trafficking and lysosome-mediated degradation of the mature, fully phosphorylated protein.
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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.