ArticleProceedings of the National Academy of Sciences of the United States of America2010
Calcineurin increases glucose activation of ERK1/2 by reversing negative feedback.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 50 citations in OpenAlex.
- Review
- The role of ERK1/2 signaling in diabetes: pathogenic and therapeutic implications.Frontiers in pharmacology · 2025Review
- Fenvalerate exposure induces AKT/AMPK-dependent alterations in glucose metabolism in hepatoma cells.Frontiers in pharmacology · 2025Article
- A web portal for exploring kinase-substrate interactions.NPJ systems biology and applications · 2024Article
- The mTOR pathway controls phosphorylation of BRAF at T401.Cell communication and signaling : CCS · 2024Article
- Navigating the ERK1/2 MAPK Cascade.Biomolecules · 2023Review
- Review
- Calcineurin inactivation inhibits pyruvate dehydrogenase complex activity and induces the Warburg effect.Oncogene · 2021Article
- CaCells · 2021Review
- Identifying New Substrates and Functions for an Old Enzyme: Calcineurin.Cold Spring Harbor perspectives in biology · 2020Review
- Trace amine-associated receptor 1 (TAAR1) promotes anti-diabetic signaling in insulin-secreting cells.The Journal of biological chemistry · 2019Article
- Friend and foe: β-cell CaMolecular metabolism · 2019Review
- Phospho-proteomic analyses of B-Raf protein complexes reveal new regulatory principles.Oncotarget · 2016Article
- Ca2+ influx through L-type Ca2+ channels and Ca2+-induced Ca2+ release regulate cAMP accumulation and Epac1-dependent ERK 1/2 activation in INS-1 cells.Molecular and cellular endocrinology · 2016Article
- Differential Regulation of ERK1/2 and mTORC1 Through T1R1/T1R3 in MIN6 Cells.Molecular endocrinology (Baltimore, Md.) · 2015Article
- Combining affinity proteomics and network context to identify new phosphatase substrates and adapters in growth pathways.Frontiers in genetics · 2014Article
- Signaling mechanisms of glucose-induced F-actin remodeling in pancreatic islet β cells.Experimental & molecular medicine · 2013Review
- Signal control through Raf: in sickness and in health.Cell research · 2012Review
- Article
- Pancreatic β-cell Raf-1 is required for glucose tolerance, insulin secretion, and insulin 2 transcription.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2011Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
In pancreatic β cells, ERK1 and ERK2 participate in nutrient sensing, and their activities rise and fall as a function of glucose concentration over the physiologic range. Glucose metabolism triggers calcium influx and release of calcium from intracellular stores to activate ERK1/2. Calcium influx also activates the calcium-dependent phosphatase calcineurin, which is required for maximal ERK1/2 activation by glucose. Calcineurin controls insulin gene expression by ERK1/2-dependent and -independent mechanisms. Here, we show that, in β cells, glucose activates the ERK1/2 cascade primarily through B-Raf. Glucose activation of B-Raf, like that of ERK1/2, is calcineurin-sensitive. Calcineurin binds to B-Raf in both unstimulated and stimulated cells. We show that B-Raf is a calcineurin substrate; among calcineurin target residues on B-Raf is T401, a site of negative feedback phosphorylation by ERK1/2. Blocking calcineurin activity in β cells prevents dephosphorylation of B-Raf T401 and decreases B-Raf and ERK1/2 activities. We conclude that the major calcineurin-dependent event in glucose sensing by ERK1/2 is the activation of B-Raf.
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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.