RGD Reference Report - Coordinated regulation by Shp2 tyrosine phosphatase of signaling events controlling insulin biosynthesis in pancreatic beta-cells. - Rat Genome Database

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Coordinated regulation by Shp2 tyrosine phosphatase of signaling events controlling insulin biosynthesis in pancreatic beta-cells.

Authors: Zhang, SS  Hao, E  Yu, J  Liu, W  Wang, J  Levine, F  Feng, GS 
Citation: Zhang SS, etal., Proc Natl Acad Sci U S A. 2009 May 5;106(18):7531-6. Epub 2009 Apr 20.
RGD ID: 2311163
Pubmed: PMID:19380737   (View Abstract at PubMed)
PMCID: PMC2678606   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.0811715106   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
promoter-specific chromatin binding  IDA 2311163 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Pdx1  (pancreatic and duodenal homeobox 1)


Additional Information