ReviewThe Biochemical journal2021
Nuts and bolts of the salt-inducible kinases (SIKs).
Review in The Biochemical journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
68 citing papers in PubMed, 114 citations in OpenAlex.
- Structure-Activity Relationship Studies Resulting in the Identification of Potent and Selective Salt-Inducible Kinase Inhibitors.ACS medicinal chemistry letters · 2026Article
- Tumor-Derived Complement C3 Overexpression in STK11-Mutant Lung Adenocarcinoma Drives Tumor Growth and Immune Checkpoint Inhibitor Resistance.Cancer immunology research · 2026Article
- Inhibition of SIK2 and SIK3 induces adaptive ER-phagy and creates a therapeutic vulnerability in ovarian cancer.Research square · 2026Article
- Targeting SIK2 with GRN-300 Potentiates Paclitaxel Efficacy in Triple-Negative Breast Cancer.Cancers · 2026Article
- Targeting hypothalamic SIK3 to promote weight loss and improve glycemic control in mice.Nature communications · 2026Article
- The Role of Protein Kinases in the Management of Oncological Diseases by Acting on Ferroptotic Pathways.International journal of molecular sciences · 2026Review
- Selective SIK2/SIK3 inhibition reprograms pro- and antiinflammatory pathways in myeloid cells, improving autoimmune disease outcomes.JCI insight · 2026Article
- Duloxetine ameliorates chronic stress-induced depressive behaviors by normalizing hippocampal SIK2-CRTC1 signaling.Frontiers in pharmacology · 2026Article
- The multimodal antidepressant vortioxetine exerts therapeutic effects in male mice which is associated with normalization of hippocampal SIK2/CRTC1-related signaling and require hippocampal CRTC1.Frontiers in pharmacology · 2026Article
- Elevated synaptic PKA activity and abnormal striatal dopamine signaling in Akap11 mutant mice, a genetic model of schizophrenia and bipolar disorder.Nature communications · 2025Article
- Elevated synaptic PKA activity and abnormal striatal dopamine signaling inbioRxiv : the preprint server for biology · 2025Article
- Class IIa HDACs Are Important Signal Transducers with Unclear Enzymatic Activities.Biomolecules · 2025Review
- Liposome-encapsulated AICAR hydrogel regulates macrophage metabolic reprogramming via SIK1 activation to alleviate osteoarthritis.Journal of nanobiotechnology · 2025Article
- The Role of the Salt-inducible Kinases in the Endocrine Glands.Endocrinology · 2025Review
- The SIK3-N783Y mutation is associated with the human natural short sleep trait.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Activation of SIK1 by phanginin A regulates skeletal muscle glucose uptake by phosphorylating HADC4/5/7 and enhancing GLUT4 expression and translocation.Natural products and bioprospecting · 2025Article
- Article
- DNAJB1-PRKACA Fusion Drives Fibrolamellar Liver Cancer through Impaired SIK Signaling and CRTC2/p300-Mediated Transcriptional Reprogramming.Cancer discovery · 2025Article
- SIK2 activates the autophagy‒apoptosis pathway through SP1 regulation to inhibit the progression of hepatocellular carcinoma.Frontiers in pharmacology · 2025Article
- Inhibition of SIK1 Alleviates the Pathologies of Psoriasis by Disrupting IL-17 Signaling.Mediators of inflammation · 2025Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The salt-inducible kinases, SIK1, SIK2 and SIK3, most closely resemble the AMP-activated protein kinase (AMPK) and other AMPK-related kinases, and like these family members they require phosphorylation by LKB1 to be catalytically active. However, unlike other AMPK-related kinases they are phosphorylated by cyclic AMP-dependent protein kinase (PKA), which promotes their binding to 14-3-3 proteins and inactivation. The most well-established substrates of the SIKs are the CREB-regulated transcriptional co-activators (CRTCs), and the Class 2a histone deacetylases (HDAC4/5/7/9). Phosphorylation by SIKs promotes the translocation of CRTCs and Class 2a HDACs to the cytoplasm and their binding to 14-3-3s, preventing them from regulating their nuclear binding partners, the transcription factors CREB and MEF2. This process is reversed by PKA-dependent inactivation of the SIKs leading to dephosphorylation of CRTCs and Class 2a HDACs and their re-entry into the nucleus. Through the reversible regulation of these substrates and others that have not yet been identified, the SIKs regulate many physiological processes ranging from innate immunity, circadian rhythms and bone formation, to skin pigmentation and metabolism. This review summarises current knowledge of the SIKs and the evidence underpinning these findings, and discusses the therapeutic potential of SIK inhibitors for the treatment of disease.
Indexed as
Identifiers
What OpenQuestion holds
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.