Phosphorylation of SNAP-25 on serine-187 is induced by secretagogues in insulin-secreting cells, but is not correlated with insulin secretion
| ISSN: | 0264-6021 |
|---|---|
| Přístupová URL adresa: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::99ca08ce3f651b771507c44b488c6c95 https://pubmed.ncbi.nlm.nih.gov/12164783 |
| Rights: | OPEN |
| Přírůstkové číslo: | edsair.doi.dedup.....99ca08ce3f651b771507c44b488c6c95 |
| Autor: | M.T. Costa, Carmen Gonelle-Gispert, Philippe A. Halban, Karin Sadoul, Masami Takahashi |
| Rok vydání: | 2002 |
| Předmět: |
Botulinum Toxins
medicine.medical_treatment Membrane Proteins/ metabolism Vesicular Transport Proteins Biochemistry PC12 Cells Serine Insulin Secretion Botulinum Toxins/pharmacology Glucose/metabolism Insulin Isoenzymes/metabolism Phosphorylation Receptor Protein Kinase C ddc:616 Tetradecanoylphorbol Acetate/pharmacology Transfection Nerve Tissue Proteins/ metabolism Isoenzymes Insulin/metabolism/secretion Tetradecanoylphorbol Acetate SNARE Proteins Research Article medicine.medical_specialty Calcium/metabolism Synaptosomal-Associated Protein 25 Protein Kinase C/metabolism Nerve Tissue Proteins Biology Exocytosis Islets of Langerhans Internal medicine medicine Animals Carbachol/pharmacology Molecular Biology Insulinoma Protein kinase C Islets of Langerhans/drug effects/metabolism Rat Insulinoma Serine/ metabolism Membrane Proteins Cell Biology medicine.disease Rats Enzyme Activation Kinetics Endocrinology Glucose nervous system Mutation Calcium Carbachol |
| Zdroj: | Biochemical Journal, Vol. 368, No Pt 1 (2002) pp. 223-232 |
| ISSN: | 0264-6021 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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