ArticleThe Journal of biological chemistry2012
Synapses of amphids defective (SAD-A) kinase promotes glucose-stimulated insulin secretion through activation of p21-activated kinase (PAK1) in pancreatic β-Cells.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 47 citations in OpenAlex.
- Further characterization of the BRSK2-associated neurodevelopmental disorder.European journal of human genetics : EJHG · 2026Article
- Role and Impact of theInternational journal of molecular sciences · 2026Article
- BRSK2 plays a role in autophagy and cancer cell growth and survival under nutrient deprivation stress via the PIK3C3 pathway.Scientific reports · 2025Article
- Gene expression changes in pancreatic α-cell lines following knock-out Of either CK2α or CK2α'.Biological research · 2025Article
- LIMK1 variants are associated with divergent endocrinological phenotypes and altered exocytosis dynamics.iScience · 2025Article
- Loss of CD98HC phosphorylation by ATM impairs antiporter trafficking and drives glutamate toxicity in Ataxia telangiectasia.Nature communications · 2025Article
- Article
- Redox Regulation of Brain Selective Kinases BRSK1/2: Implications for Dynamic Control of the Eukaryotic AMPK family through Cys-based mechanisms.bioRxiv : the preprint server for biology · 2024Article
- BRSK2 in pancreatic β cells promotes hyperinsulinemia-coupled insulin resistance and its genetic variants are associated with human type 2 diabetes.Journal of molecular cell biology · 2023Article
- Regulation of insulin secretion by the post-translational modifications.Frontiers in cell and developmental biology · 2023Review
- AMPKα-like proteins as LKB1 downstream targets in cell physiology and cancer.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Gain-of-function genetic screen of the kinome reveals BRSK2 as an inhibitor of the NRF2 transcription factor.Journal of cell science · 2020Article
- Cdc42: A Novel Regulator of Insulin Secretion and Diabetes-Associated Diseases.International journal of molecular sciences · 2019Review
- SAD-A Promotes Glucose-Stimulated Insulin Secretion Through Phosphorylation and Inhibition of GDIα in Male Islet β Cells.Endocrinology · 2018Article
- Selection of growth-related genes and dominant genotypes in transgenic Yellow River carp Cyprinus carpio L.Functional & integrative genomics · 2018Article
- Pak1 mediates the stimulatory effect of insulin and curcumin on hepatic ChREBP expression.Journal of molecular cell biology · 2017Article
- Structural insight into the mechanism of synergistic autoinhibition of SAD kinases.Nature communications · 2015Article
- Cardiolipin remodeling by TAZ/tafazzin is selectively required for the initiation of mitophagy.Autophagy · 2015Article
- New insights concerning the molecular basis for defective glucoregulation in soluble adenylyl cyclase knockout mice.Biochimica et biophysica acta · 2014Review
- YES, a Src family kinase, is a proximal glucose-specific activator of cell division cycle control protein 42 (Cdc42) in pancreatic islet β cells.The Journal of biological chemistry · 2014Article
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
The p21-activated kinase-1 (PAK1) is implicated in regulation of insulin exocytosis as an effector of Rho GTPases. PAK1 is activated by the onset of glucose-stimulated insulin secretion (GSIS) through phosphorylation of Thr-423, a major activation site by Cdc42 and Rac1. However, the kinase(s) that phosphorylates PAK1 at Thr-423 in islet β-cells remains elusive. The present studies identified SAD-A (synapses of amphids defective), a member of AMP-activated protein kinase-related kinases exclusively expressed in brain and pancreas, as a key regulator of GSIS through activation of PAK1. We show that SAD-A directly binds to PAK1 through its kinase domain. The interaction is mediated by the p21-binding domain (PBD) of PAK1 and requires both kinases in an active conformation. The binding leads to direct phosphorylation of PAK1 at Thr-423 by SAD-A, triggering the onset of GSIS from islet β-cells. Consequently, ablation of PAK1 kinase activity or depletion of PAK1 expression completely abolishes the potentiating effect of SAD-A on GSIS. Consistent with its role in regulating GSIS, overexpression of SAD-A in MIN6 islet β-cells significantly stimulated cytoskeletal remodeling, which is required for insulin exocytosis. Together, the present studies identified a critical role of SAD-A in the activation of PAK1 during the onset of insulin exocytosis.
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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.