ArticlePloS one2017
Analysis of a cAMP regulated coactivator family reveals an alternative phosphorylation motif for AMPK family members.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- Hepatic glycogen directly regulates gluconeogenesis through an AMPK/CRTC2 axis in mice.The Journal of clinical investigation · 2025Article
- Regulation of Sleep Amount by CRTC1 via Transcription ofThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Petanin Potentiated JNK Phosphorylation to Negatively Regulate the ERK/CREB/MITF Signaling Pathway for Anti-Melanogenesis in Zebrafish.International journal of molecular sciences · 2024Article
- Identification of gene isoforms and their switching events between male and female embryos of the parthenogenetic crustacean Daphnia magna.Scientific reports · 2024Article
- Targeting phosphorylation circuits on CREB and CRTCs as the strategy to prevent acquired skin hyperpigmentation.International journal of biological sciences · 2024Article
- Reduced miR-184-3p expression protects pancreatic β-cells from lipotoxic and proinflammatory apoptosis in type 2 diabetes via CRTC1 upregulation.Cell death discovery · 2022Article
- New Insights Into the Pivotal Role of CREB-Regulated Transcription Coactivator 1 in Depression and Comorbid Obesity.Frontiers in molecular neuroscience · 2022Review
- Transcriptional co-activator regulates melanocyte differentiation and oncogenesis by integrating cAMP and MAPK/ERK pathways.Cell reports · 2021Article
- Nuts and bolts of the salt-inducible kinases (SIKs).The Biochemical journal · 2021Review
- Loss of the conserved PKA sites of SIK1 and SIK2 increases sleep need.Scientific reports · 2020Article
- Salt-inducible kinases (SIKs) regulate TGFβ-mediated transcriptional and apoptotic responses.Cell death & disease · 2020Article
- The CREB coactivator CRTC2 promotes oncogenesis in LKB1-mutant non-small cell lung cancer.Science advances · 2019Article
- Adaptive Transcriptional Responses by CRTC Coactivators in Cancer.Trends in cancer · 2019Review
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- Inhibition by fluoxetine of LH-stimulated cyclic AMP synthesis in tumor Leydig cells partly involves AMPK activation.PloS one · 2019Article
- Salt-Inducible Kinases: Physiology, Regulation by cAMP, and Therapeutic Potential.Trends in endocrinology and metabolism: TEM · 2018Review
- Cyclic adenosine monophosphate-regulated transcriptional co-activator 3 polymorphism in Chinese patients with acute coronary syndrome.Medicine · 2018Observational
- cAMP-inducible coactivator CRTC3 attenuates brown adipose tissue thermogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Cholesterol signaling in single cells: lessons from STAR and sm-FISH.Journal of molecular endocrinology · 2018Review
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
The second messenger cAMP stimulates cellular gene expression via the PKA-mediated phosphorylation of the transcription factor CREB and through dephosphorylation of the cAMP-responsive transcriptional coactivators (CRTCs). Under basal conditions, CRTCs are phosphorylated by members of the AMPK family of Ser/Thr kinases and sequestered in the cytoplasm via a phosphorylation-dependent association with 14-3-3 proteins. Increases in cAMP promote the dephosphorylation and nuclear translocation of CRTCs, where they bind to CREB and stimulate relevant target genes. Although they share considerable sequence homology, members of the CRTC family exert non-overlapping effects on cellular gene expression through as yet unidentified mechanisms. Here we show that the three CRTCs exhibit distinct patterns of 14-3-3 binding at three conserved sites corresponding to S70, S171, and S275 (in CRTC2). S171 functions as the gatekeeper site for 14-3-3 binding; it acts cooperatively with S275 in stabilizing this interaction following its phosphorylation by the cAMP-responsive SIK and the cAMP-nonresponsive MARK kinases. Although S171 contains a consensus recognition site for phosphorylation by AMPK family members, S70 and S275 carry variant motifs (MNTGGS275LPDL), lacking basic residues that are otherwise critical for SIK/MARK recognition as well as 14-3-3 binding. Correspondingly, the activity of these motifs differs between CRTC family members. As the variant (SLPDL) motif is present and apparently phosphorylated in other mammalian proteins, our studies suggest that the regulation of cellular targets by AMPK family members is more extensive than previously appreciated.
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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.