ArticleThe Journal of biological chemistry2015
The paired basic amino acid-cleaving enzyme 4 (PACE4) is involved in the maturation of insulin receptor isoform B: an opportunity to reduce the specific insulin receptor-dependent effects of insulin-like growth factor 2 (IGF2).
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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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
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- A Genome-Wide Association Study of Prediabetes Status Change.Frontiers in endocrinology · 2022Pooled it
- Proprotein Convertase Subtilisin/Kexin 6 in Cardiovascular Biology and Disease.International journal of molecular sciences · 2022Review
- Review
- Toward the Decipherment of Molecular Interactions in the Diabetic Brain.Biomedicines · 2022Review
- Proprotein Convertases and the Complement System.Frontiers in immunology · 2022Review
- The aminosterol Claramine inhibits β-secretase 1-mediated insulin receptor cleavage.The Journal of biological chemistry · 2021Article
- Differential Effects ofInternational journal of molecular sciences · 2021Article
- Mouse Models of Human Proprotein Convertase Insufficiency.Endocrine reviews · 2021Review
- Insulin and Insulin Receptors in Adipose Tissue Development.International journal of molecular sciences · 2019Review
- Proprotein convertase furin regulates osteocalcin and bone endocrine function.The Journal of clinical investigation · 2017Article
- Insulin Receptor Isoforms in Physiology and Disease: An Updated View.Endocrine reviews · 2017Review
- Insulin Resistance: Any Role in the Changing Epidemiology of Thyroid Cancer?Frontiers in endocrinology · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gaining the full activity of the insulin receptor (IR) requires the proteolytic cleavage of its proform by intra-Golgi furin-like activity. In mammalian cells, IR is expressed as two isoforms (IRB and IRA) that are responsible for insulin action. However, only IRA transmits the growth-promoting and mitogenic effects of insulin-like growth factor 2. Here we demonstrate that the two IR isoforms are similarly cleaved by furin, but when this furin-dependent maturation is inefficient, IR proforms move to the cell surface where the proprotein convertase PACE4 selectively supports IRB maturation. Therefore, in situations of impaired furin activity, the proteolytic maturation of IRB is greater than that of IRA, and accordingly, the amount of phosphorylated IRB is also greater than that of IRA. We highlight the ability of a particular proprotein convertase inhibitor to effectively reduce the maturation of IRA and its associated mitogenic signaling without altering the signals emanating from IRB. In conclusion, the selective PACE4-dependent maturation of IRB occurs when furin activity is reduced; accordingly, the pharmacological inhibition of furin reduces IRA maturation and its mitogenic potential without altering the insulin effects.
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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.