Phosphorylation of SNAP-23 regulates exocytosis from mast cells.
J Biol Chem
; 280(8): 6610-20, 2005 Feb 25.
Article
em En
| MEDLINE
| ID: mdl-15611044
ABSTRACT
Regulated exocytosis is a process in which a physiological trigger initiates the translocation, docking, and fusion of secretory granules with the plasma membrane. A class of proteins termed SNAREs (including SNAP-23, syntaxins, and VAMPs) are known regulators of secretory granule/plasma membrane fusion events. We have investigated the molecular mechanisms of regulated exocytosis in mast cells and find that SNAP-23 is phosphorylated when rat basophilic leukemia mast cells are triggered to degranulate. The kinetics of SNAP-23 phosphorylation mirror the kinetics of exocytosis. We have identified amino acid residues Ser(95) and Ser(120) as the major phosphorylation sites in SNAP-23 in rodent mast cells. Quantitative analysis revealed that approximately 10% of SNAP-23 was phosphorylated when mast cell degranulation was induced. These same residues were phosphorylated when mouse platelet degranulation was induced with thrombin, demonstrating that phosphorylation of SNAP-23 Ser(95) and Ser(120) is not restricted to mast cells. Although triggering exocytosis did not alter the absolute amount of SNAP-23 bound to SNAREs, after stimulation essentially all of the SNAP-23 bound to the plasma membrane SNARE syntaxin 4 and the vesicle SNARE VAMP-2 was phosphorylated. Regulated exocytosis studies revealed that overexpression of SNAP-23 phosphorylation mutants inhibited exocytosis from rat basophilic leukemia mast cells, demonstrating that phosphorylation of SNAP-23 on Ser(120) and Ser(95) modulates regulated exocytosis by mast cells.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Transporte Vesicular
/
Exocitose
/
Mastócitos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Estados Unidos