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Title

Phosphorylation of SNAP-25 on serine-187 is induced by secretagogues in insulin-secreting cells, but is not correlated with insulin secretion

Authors
Costa, Maria
Takahashi, Masami
Published in Biochemical Journal. 2002, vol. 368, no. Pt 1, p. 223-232
Abstract The tSNARE (the target-membrane soluble NSF-attachment protein receptor, where NSF is N -ethylmaleimide-sensitive fusion protein) synaptosomal-associated protein of 25 kDa (SNAP-25) is implicated in regulated insulin secretion. In pheochromocytoma PC12 cells, SNAP-25 is phosphorylated at Ser(187), which lies in a region that is important for its function. The aims of the present study were to determine whether SNAP-25 is phosphorylated at Ser(187) in insulin-secreting cells and, if so, whether this is important for regulated insulin secretion. The major findings are: (i) SNAP-25 is rapidly and reversibly phosphorylated on Ser(187) in both rat insulinoma INS-1 cells and rat islets in response to the phorbol ester, PMA; (ii) less than 35% of SNAP-25 in INS-1 cells is phosphorylated in response to PMA, and phosphorylation is limited to plasma-membrane-associated SNAP-25; (iii) both SNAP-25 isoforms (a and b) are phosphorylated, with 1.8-fold greater phosphorylation for SNAP-25b in response to PMA; (iv) in rat islets, Ser(187) phosphorylation is stimulated by glucose or carbachol, albeit to a lesser extent than by PMA, but not by cAMP; (v) insulin secretion from botulinum neurotoxin E-treated hamster insulinoma tumour (HIT) cells, transfected with toxin-resistant Ser(187)-->Ala or Ser(187)-->Asp mutant SNAP-25, was similar to that of wild-type HIT cells. Furthermore, in rat islets no correlation was found between the extent of SNAP-25 phosphorylation at Ser(187) in response to secretagogues and stimulation of insulin release; (vi) use of protein kinase C (PKC) inhibitors suggests that glucose stimulates SNAP-25 phosphorylation via conventional and non-conventional PKC isoforms. In summary, although SNAP-25 phosphorylation at Ser(187) occurs in insulin-secreting cells and is mediated by PKC, it does not appear to play a major role in regulated insulin secretion.
Keywords AnimalsBotulinum Toxins/pharmacologyCalcium/metabolismCarbachol/pharmacologyEnzyme ActivationExocytosisGlucose/metabolismInsulin/metabolism/secretionIslets of Langerhans/drug effects/metabolismIsoenzymes/metabolismKineticsMembrane Proteins/ metabolismMutationNerve Tissue Proteins/ metabolismPC12 CellsPhosphorylationProtein Kinase C/metabolismRatsSNARE ProteinsSerine/ metabolismSynaptosomal-Associated Protein 25Tetradecanoylphorbol Acetate/pharmacologyVesicular Transport Proteins
Identifiers
PMID: 12164783
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GONELLE-GISPERT, Carmen et al. Phosphorylation of SNAP-25 on serine-187 is induced by secretagogues in insulin-secreting cells, but is not correlated with insulin secretion. In: Biochemical Journal, 2002, vol. 368, n° Pt 1, p. 223-232. https://archive-ouverte.unige.ch/unige:8760

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Deposited on : 2010-07-12

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