Scientific article

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

Published inBiochemical journal, vol. 368, no. Pt 1, p. 223-232
Publication date2002

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.

  • Animals
  • Botulinum Toxins/pharmacology
  • Calcium/metabolism
  • Carbachol/pharmacology
  • Enzyme Activation
  • Exocytosis
  • Glucose/metabolism
  • Insulin/metabolism/secretion
  • Islets of Langerhans/drug effects/metabolism
  • Isoenzymes/metabolism
  • Kinetics
  • Membrane Proteins/ metabolism
  • Mutation
  • Nerve Tissue Proteins/ metabolism
  • PC12 Cells
  • Phosphorylation
  • Protein Kinase C/metabolism
  • Rats
  • SNARE Proteins
  • Serine/ metabolism
  • Synaptosomal-Associated Protein 25
  • Tetradecanoylphorbol Acetate/pharmacology
  • Vesicular Transport Proteins
Citation (ISO format)
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. doi: 10.1042/BJ20020896
Updates (1)
ISSN of the journal0264-6021

Technical informations

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