ArticleJournal of cell science2015
SIK2 regulates CRTCs, HDAC4 and glucose uptake in adipocytes.
Article in Journal of cell science, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 88 citations in OpenAlex.
- Low-Coverage Whole-Genome Analysis of Population Structure, Bottlenecks, and Selection in Indiana Bats Before and After White-Nose Syndrome.Molecular ecology · 2025Article
- SIK2 Drives Pulmonary Fibrosis by Enhancing Fibroblast Glycolysis and Activation.Biomedicines · 2025Article
- HDAC4: an emerging target in diabetes mellitus and diabetic complications.European journal of medical research · 2025Review
- Salt-inducible Kinase Regulation of Adipose Tissue Metabolism.Endocrinology · 2025Review
- Roles of Histone Deacetylase 4 in the Inflammatory and Metabolic Processes.Diabetes & metabolism journal · 2024Review
- AMPK and Beyond: The Signaling Network Controlling RabGAPs and Contraction-Mediated Glucose Uptake in Skeletal Muscle.International journal of molecular sciences · 2024Review
- Understanding the roles of salt-inducible kinases in cardiometabolic disease.Frontiers in physiology · 2024Review
- The multiple roles of salt-inducible kinases in regulating physiology.Physiological reviews · 2023Review
- Mechanism of TNFα-induced downregulation of salt-inducible kinase 2 in adipocytes.Scientific reports · 2023Article
- Histone deacetylase 7: a signalling hub controlling development, inflammation, metabolism and disease.The FEBS journal · 2023Review
- Designing of potent anti-diabetic molecules by targeting SIK2 using computational approaches.Molecular diversity · 2023Article
- The role of liver kinase B1 in tumor progression through regulation of lipid metabolism.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Review
- Salt-inducible kinase 3 protects tumor cells from cytotoxic T-cell attack by promoting TNF-induced NF-κB activation.Journal for immunotherapy of cancer · 2022Article
- SIK2 kinase synthetic lethality is driven by spindle assembly defects in FANCA-deficient cells.Molecular oncology · 2022Article
- Activation of the adipocyte CREB/CRTC pathway in obesity.Communications biology · 2021Article
- Salt-Inducible Kinase 3 Promotes Vascular Smooth Muscle Cell Proliferation and Arterial Restenosis by Regulating AKT and PKA-CREB Signaling.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- Article
- Nuts and bolts of the salt-inducible kinases (SIKs).The Biochemical journal · 2021Review
- Comprehensive evaluation of the metabolic effects of porcine CRTC3 overexpression on subcutaneous adipocytes with metabolomic and transcriptomic analyses.Journal of animal science and biotechnology · 2021Article
- Phosphoproteomic identification of vasopressin-regulated protein kinases in collecting duct cells.British journal of pharmacology · 2021Article
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Authors and funding
13 authors at 5 institutions in 4 countries.
Funding
Abstract
Salt-inducible kinase 2 (SIK2) is an AMP-activated protein kinase (AMPK) related kinase abundantly expressed in adipose tissue. Our aim was to identify molecular targets and functions of SIK2 in adipocytes, and to address the role of PKA-mediated phosphorylation of SIK2 on Ser358. Modulation of SIK2 in adipocytes resulted in altered phosphorylation of CREB-regulated transcription co-activator 2 (CRTC2), CRTC3 and class IIa histone deacetylase 4 (HDAC4). Furthermore, CRTC2, CRTC3, HDAC4 and protein phosphatase 2A (PP2A) interacted with SIK2, and the binding of CRTCs and PP2A to wild-type but not Ser358Ala SIK2, was reduced by cAMP elevation. Silencing of SIK2 resulted in reduced GLUT4 (also known as SLC2A4) protein levels, whereas cells treated with CRTC2 or HDAC4 siRNA displayed increased levels of GLUT4. Overexpression or pharmacological inhibition of SIK2 resulted in increased and decreased glucose uptake, respectively. We also describe a SIK2–CRTC2–HDAC4 pathway and its regulation in human adipocytes, strengthening the physiological relevance of our findings. Collectively, we demonstrate that SIK2 acts directly on CRTC2, CRTC3 and HDAC4, and that the cAMP–PKA pathway reduces the interaction of SIK2 with CRTCs and PP2A. Downstream, SIK2 increases GLUT4 levels and glucose uptake in adipocytes.
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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.