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PMID:17448994

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Citation

Konstantinova, I, Nikolova, G, Ohara-Imaizumi, M, Meda, P, Kucera, T, Zarbalis, K, Wurst, W, Nagamatsu, S and Lammert, E (2007) EphA-Ephrin-A-mediated beta cell communication regulates insulin secretion from pancreatic islets. Cell 129:359-70

Abstract

In vertebrates, beta cells are aggregated in the form of pancreatic islets. Within these islets, communication between beta cells inhibits basal insulin secretion and enhances glucose-stimulated insulin secretion, thus contributing to glucose homeostasis during fasting and feeding. In the search for the underlying molecular mechanism, we have discovered that beta cells communicate via ephrin-As and EphAs. We provide evidence that ephrin-A5 is required for glucose-stimulated insulin secretion. We further show that EphA-ephrin-A-mediated beta cell communication is bidirectional: EphA forward signaling inhibits insulin secretion, whereas ephrin-A reverse signaling stimulates insulin secretion. EphA forward signaling is downregulated in response to glucose, which indicates that, under basal conditions, beta cells use EphA forward signaling to suppress insulin secretion and that, under stimulatory conditions, they shift to ephrin-A reverse signaling to enhance insulin secretion. Thus, we explain how beta cell communication in pancreatic islets conversely affects basal and glucose-stimulated insulin secretion to improve glucose homeostasis.

Links

PubMed Online version:10.1016/j.cell.2007.02.044

Keywords

Animals; Cell Communication; Cell Line; Ephrin-A5/metabolism; Ephrins/metabolism; Female; Glucose/metabolism; Humans; Insulin/secretion; Insulin-Secreting Cells/metabolism; Islets of Langerhans/metabolism; Islets of Langerhans/secretion; Male; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Phosphorylation; Receptors, Eph Family/metabolism; Signal Transduction

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:EFNA5

involved_in

GO:0032956: regulation of actin cytoskeleton organization

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:EFNA5

located_in

GO:0005886: plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:EFNA5

involved_in

GO:0050731: positive regulation of peptidyl-tyrosine phosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:EFNA5

involved_in

GO:0048013: ephrin receptor signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:EFNA5

involved_in

GO:0061178: regulation of insulin secretion involved in cellular response to glucose stimulus

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:EFNA5

involved_in

GO:0043087: regulation of GTPase activity

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:EPHA5

involved_in

GO:0032956: regulation of actin cytoskeleton organization

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:EPHA5

enables

GO:0005004: GPI-linked ephrin receptor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:EPHA5

involved_in

GO:0048013: ephrin receptor signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:EPHA5

involved_in

GO:0061178: regulation of insulin secretion involved in cellular response to glucose stimulus

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:EPHA5

involved_in

GO:0043087: regulation of GTPase activity

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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