ArticleProceedings of the National Academy of Sciences of the United States of America2009
Coordinated regulation by Shp2 tyrosine phosphatase of signaling events controlling insulin biosynthesis in pancreatic beta-cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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Who cites it
28 citing papers in PubMed, 46 citations in OpenAlex.
- Type 1 diabetesNPJ autoimmunity · 2026Article
- Chronic Exposure to Environmentally Relevant Concentrations of Tetracycline Perturbs Gut Homeostasis in Zebrafish.Environment & health (Washington, D.C.) · 2023Article
- Structural insights into the pSer/pThr dependent regulation of the SHP2 tyrosine phosphatase in insulin and CD28 signaling.Nature communications · 2022Article
- The Tyrosine Phosphatase SHP2: A New Target for Insulin Resistance?Biomedicines · 2022Review
- Article
- The Immunoregulatory Role of the Signal Regulatory Protein Family and CD47 Signaling Pathway in Type 1 Diabetes.Frontiers in immunology · 2021Review
- Tectorigenin enhances PDX1 expression and protects pancreatic β-cells by activating ERK and reducing ER stress.The Journal of biological chemistry · 2020Article
- Mitotic regulators and the SHP2-MAPK pathway promote IR endocytosis and feedback regulation of insulin signaling.Nature communications · 2019Article
- Loss of Shp2 Rescues BDNF/TrkB Signaling and Contributes to Improved Retinal Ganglion Cell Neuroprotection.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- SH2 Domain-Containing Phosphatase-2 Is a Novel Antifibrotic Regulator in Pulmonary Fibrosis.American journal of respiratory and critical care medicine · 2017Article
- A Cross-Species Study of PI3K Protein-Protein Interactions Reveals the Direct Interaction of P85 and SHP2.Scientific reports · 2016Article
- New and Unexpected Biological Functions for the Src-Homology 2 Domain-Containing Phosphatase SHP-2 in the Gastrointestinal Tract.Cellular and molecular gastroenterology and hepatology · 2016Review
- Shp2 suppresses the adipogenic differentiation of preadipocyte 3T3-L1 cells at an early stage.Cell death discovery · 2016Article
- Hexane Extract of Orthosiphon stamineus Induces Insulin Expression and Prevents Glucotoxicity in INS-1 Cells.Diabetes & metabolism journal · 2015Article
- Pancreatic T cell protein-tyrosine phosphatase deficiency affects beta cell function in mice.Diabetologia · 2015Article
- LEOPARD syndrome-associated SHP2 mutation confers leanness and protection from diet-induced obesity.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Disruption of protein-tyrosine phosphatase 1B expression in the pancreas affects β-cell function.Endocrinology · 2014Article
- SH2B1 in β-cells promotes insulin expression and glucose metabolism in mice.Molecular endocrinology (Baltimore, Md.) · 2014Article
- Metabolic regulation by protein tyrosine phosphatases.Journal of biomedical research · 2014Article
- S-nitrosylated SHP-2 contributes to NMDA receptor-mediated excitotoxicity in acute ischemic stroke.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Intracellular signaling by which pancreatic beta-cells synthesize and secrete insulin in control of glucose homeostasis is not fully understood. Here we show that Shp2, a cytoplasmic tyrosine phosphatase possessing 2 SH2 domains, coordinates signaling events required for insulin biosynthesis in beta-cells. Mice with conditional ablation of the Shp2/Ptpn11 gene in the pancreas exhibited defective glucose-stimulated insulin secretion and impaired glucose tolerance. Consistently, siRNA-mediated Shp2-knockdown in rat insulinoma INS-1 832/13 cells resulted in decreased insulin production and secretion despite an increase in cellular ATP. Shp2 modulates the strength of signals flowing through Akt/FoxO1 and Erk pathways, culminating in control of Pdx1 expression and activity on Ins1 and Ins2 promoters, and forced Pdx1 expression rescued insulin production in Shp2-knockdown beta-cells. Therefore, Shp2 acts as a signal coordinator in beta-cells, orchestrating multiple pathways controlling insulin biosynthesis to maintain glucose homeostasis.
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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.