KEPI, a PKC-dependent protein phosphatase 1 inhibitor regulated by morphine
Open accessAbstract
cDNAs encoding KEPI, a novel protein kinase C (PKC)-potentiated inhibitory protein for type 1 Ser/Thr protein phosphatase (PP1), were identified. They were found among morphine-regulated brain mRNAs identified using subtracted differential display techniques. Full-length rat, mouse, and human cDNA and genomic sequences were elucidated with library screening and data base searching. Rat, mouse, and human KEPI cDNAs encode 164-165 amino acid proteins with calculated isoelectric points of 5.2. Each species' amino acid sequence contains consensus sequences for phosphorylation by PKC (KVT(72)VK), protein kinase A (RKLS(154)), and casein kinase II (S(43)SRE, S(120)EEE). Multiple KEPI N-terminal myristoylation consensus sites provide potential regions for membrane anchoring. Subcellular fractionation and Western analyses revealed that most KEPI immunoreactivity was associated with P2 and P3 membrane-enriched fractions and little in cytosolic fractions. 2.6-kb KEPI mRNAs were detected in brain, especially in the cerebral cortex and hippocampus, and in heart and skeletal muscle. Brain KEPI mRNA was up-regulated by both acute and chronic morphine treatments. The human KEPI gene contains four exons extending over more than 100 kb of genomic sequence on 6q24-q25, near the mu opiate receptor gene. These sequences displayed sufficient homology with the porcine PP1 inhibitor CPI-17 that we asked whether KEPI could share the ability of CPI-17 to modulate PP1 activity in a PKC-dependent fashi…
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The PPP1R14C gene could play an important role in the tolerance mechanisms of Sheko with PP1, a competitive inhibitor of ATP binding of Src tyrosine kinase family members.
“Interestingly, the PPP1R14C gene could play an important role in the tolerance mechanisms of Sheko with PP1, a competitive inhibitor of ATP binding of Src tyrosine kinase family members (Hanke et al., 1996; Liu et al., 2002).”
From Identification of Candidate Signature Genes and Key Regulators Associated With Trypanotolerance in the Sheko Breed (2019) · cites this paper as Liu et al., 2002
Activated AKT is a mediator of neuronal cell survival.
“In addition, activated AKT is a mediator of neuronal cell survival (Liu et al., 2002; Chen et al., 2003; Pulst, 2016).”
From Identification of Candidate Signature Genes and Key Regulators Associated With Trypanotolerance in the Sheko Breed (2019) · cites this paper as Liu et al., 2002
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Mekonnen, Y. A., Gültas, M., Effa, K., Hanotte, O., & Schmitt, A. O. (2019) · Frontiers in Genetics · doi:10.3389/fgene.2019.01095 · Cited by 37 · see citing works
- Authors
- Liu, Q.-R., Zhang, P.-W., Zhen, Q., Walther, D., Wang, X.-B., & Uhl, G. R.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Uhl, George R.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2002-04
- Volume
- 277
- Issue
- 15
- Pages
- 13312-13320
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2051742466
- Cited by
- 71
- References
- 0
- Citations by year
- 2026: 3 · 2025: 4 · 2023: 1 · 2022: 5 · 2021: 2 · 2020: 4 · 2019: 2 · 2018: 2 · 2017: 2 · 2016: 1 · 2015: 2 · 2014: 5 · 2013: 3 · 2012: 3
- FWCI
- 1.97
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Keywords
- protein kinase C, morphine, mu-opioid receptor, G protein-coupled receptor signaling, protein phosphorylation, CPI-17, myristoylation, brain gene expression, chronic morphine administration, PP1α, protein phosphatase 2A, cDNA cloning, gene structure
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Enzyme Inhibitors, Humans, Male, Membrane Proteins, Mice, Inbred C57BL, Molecular Sequence Data, Morphine, Phosphoprotein Phosphatases, Phosphorylation, Polymorphism, Genetic, Protein Kinase C, Proteins, RNA, Messenger, Signal Transduction, Up-Regulation, Rats, Sprague-Dawley, Sequence Homology, Amino Acid, DNA, Complementary, Mice, Knockout, Intracellular Signaling Peptides and Proteins, Mice, Rats, Protein Phosphatase 1, Protein Phosphatase 2
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