ArticleMolecular and cellular biology1999
Activation of IkappaB kinase beta by protein kinase C isoforms.
Article in Molecular and cellular biology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
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Who cites it
92 citing papers in PubMed, 361 citations in OpenAlex.
- The Role of Protein Kinase C During the Differentiation of Stem and Precursor Cells into Tissue Cells.Biomedicines · 2024Review
- Equine Embryonic Stem Cell-Derived Tenocytes are Insensitive to a Combination of Inflammatory Cytokines and Have Distinct Molecular Responses Compared to Primary Tenocytes.Stem cell reviews and reports · 2024Article
- The function of serine/threonine-specific protein kinases in B cells.Frontiers in immunology · 2024Review
- Novel components in the nuclear factor-kappa B (NF-κB) signaling pathways of endothelial cells under hyperglycemic-ischemic conditions.Frontiers in cardiovascular medicine · 2024Article
- RNA demethylase ALKBH5 suppresses tumorigenesis via inhibiting proliferation and invasion and promoting CD8Translational oncology · 2023Article
- Atypical protein kinase C is essential for embryonic vascular development in mice.Genesis (New York, N.Y. : 2000) · 2021Article
- Adiponectin restrains ILC2 activation by AMPK-mediated feedback inhibition of IL-33 signaling.The Journal of experimental medicine · 2021Article
- NF-κB/Rel Transcription Factors in Pancreatic Cancer: Focusing on RelA, c-Rel, and RelB.Cancers · 2019Review
- Combined Hyperglycemia- and Hyperinsulinemia-Induced Insulin Resistance in Adipocytes Is Associated With Dual Signaling Defects Mediated by PKC-ζ.Endocrinology · 2018Article
- Latent Inflammation and Insulin Resistance in Adipose Tissue.International journal of endocrinology · 2017Review
- Signaling via the NFκB system.Wiley interdisciplinary reviews. Systems biology and medicine · 2016Review
- Suppression of TPA-induced cancer cell invasion by Peucedanum japonicum Thunb. extract through the inhibition of PKCα/NF-κB-dependent MMP-9 expression in MCF-7 cells.International journal of molecular medicine · 2016Article
- Signal transduction in inherited metabolic disorders: a model for a possible pathogenetic mechanism.Journal of inherited metabolic disease · 2015Review
- Loss of the polarity protein PAR3 activates STAT3 signaling via an atypical protein kinase C (aPKC)/NF-κB/interleukin-6 (IL-6) axis in mouse mammary cells.The Journal of biological chemistry · 2015Article
- Depression of testes-specific protease 50 (TSP50) inhibits cell proliferation and induces apoptosis in laryngocarcinoma.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
- Redox control of microglial function: molecular mechanisms and functional significance.Antioxidants & redox signaling · 2014Review
- PKCλ haploinsufficiency prevents diabetes by a mechanism involving alterations in hepatic enzymes.Molecular endocrinology (Baltimore, Md.) · 2014Article
- A splicing variant of NME1 negatively regulates NF-κB signaling and inhibits cancer metastasis by interacting with IKKβ.The Journal of biological chemistry · 2014Article
- Short-term Mg deficiency upregulates protein kinase C isoforms in cardiovascular tissues and cells; relation to NF-kB, cytokines, ceramide salvage sphingolipid pathway and PKC-zeta: hypothesis and review.International journal of clinical and experimental medicine · 2014Article
- Article
32 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
The atypical protein kinase C (PKC) isotypes (lambda/iotaPKC and zetaPKC) have been shown to be critically involved in important cell functions such as proliferation and survival. Previous studies have demonstrated that the atypical PKCs are stimulated by tumor necrosis factor alpha (TNF-alpha) and are required for the activation of NF-kappaB by this cytokine through a mechanism that most probably involves the phosphorylation of IkappaB. The inability of these PKC isotypes to directly phosphorylate IkappaB led to the hypothesis that zetaPKC may use a putative IkappaB kinase to functionally inactivate IkappaB. Recently several groups have molecularly characterized and cloned two IkappaB kinases (IKKalpha and IKKbeta) which phosphorylate the residues in the IkappaB molecule that serve to target it for ubiquitination and degradation. In this study we have addressed the possibility that different PKCs may control NF-kappaB through the activation of the IKKs. We report here that alphaPKC as well as the atypical PKCs bind to the IKKs in vitro and in vivo. In addition, overexpression of zetaPKC positively modulates IKKbeta activity but not that of IKKalpha, whereas the transfection of a zetaPKC dominant negative mutant severely impairs the activation of IKKbeta but not IKKalpha in TNF-alpha-stimulated cells. We also show that cell stimulation with phorbol 12-myristate 13-acetate activates IKKbeta, which is entirely dependent on the activity of alphaPKC but not that of the atypical isoforms. In contrast, the inhibition of alphaPKC does not affect the activation of IKKbeta by TNF-alpha. Interestingly, recombinant active zetaPKC and alphaPKC are able to stimulate in vitro the activity of IKKbeta but not that of IKKalpha. In addition, evidence is presented here that recombinant zetaPKC directly phosphorylates IKKbeta in vitro, involving Ser177 and Ser181. Collectively, these results demonstrate a critical role for the PKC isoforms in the NF-kappaB pathway at the level of IKKbeta activation and IkappaB degradation.
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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.