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12130572

Source:http://linkedlifedata.com/resource/pubmed/id/12130572

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pubmed-article:12130572pubmed:abstractTextAnnexin 1 (ANXA1) is an important mediator of glucocorticoid action in the neuroendocrine system. As the activity of this protein in other systems is modulated by phosphorylation of its N-terminal domain, we have explored the significance of this domain and its phosphorylation status to ANXA1 actions within the pituitary gland, using an established in vitro preparation. Two N-terminal peptides, ANXA1(Ac2-26) and ANXA1(Ac1-50), inhibited forskolin-evoked ACTH and prolactin release; however, they lacked the potency and full efficacy of the parent molecule (ANXA1(1-346)), whereas other shorter N-terminal sequences were without effect. A chimeric protein comprising ANXA1(1-44) and the C-terminal core of ANXA5 (ANXA5(20-320)) also produced a partial inhibition of peptide release. Protein kinase C (PKC) blockade (PKC(19-36)) abolished the inhibitory effects of dexamethasone on forskolin-evoked peptide release and attenuated the antisecretory actions of ANXA1(Ac2-26.) ANXA5, which sequesters PKC in other systems, produced similar effects. PKC(19-36) also blocked the dexamethasone- induced translocation of a serine phosphorylated species of ANXA1 from the cytoplasm to the outer cell surface. These results suggest that 1) the N-terminal domain plays a fundamental role in effecting the inhibitory actions of ANXA1 on pituitary peptide release; 2) PKC-dependent mechanisms are essential for both the cellular exportation and the biological activity of ANXA1; and 3) ANXA1 exported from the cells is serine phosphorylated.lld:pubmed
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pubmed-article:12130572pubmed:dateRevised2007-11-15lld:pubmed
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pubmed-article:12130572pubmed:articleTitleAnnexin 1-dependent actions of glucocorticoids in the anterior pituitary gland: roles of the N-terminal domain and protein kinase C.lld:pubmed
pubmed-article:12130572pubmed:affiliationDepartment of Neuroendocrinology, Division of Neuroscience and Psychological Medicine, Faculty of Medicine, Imperial College of Science Technology and Medicine, Hammersmith Hospital Campus, Du Cane Road, London W12 ONN, UK.lld:pubmed
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