Source:http://linkedlifedata.com/resource/pubmed/id/12130572
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
8
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pubmed:dateCreated |
2002-7-19
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pubmed:abstractText |
Annexin 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.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adrenocorticotropic Hormone,
http://linkedlifedata.com/resource/pubmed/chemical/Annexin A1,
http://linkedlifedata.com/resource/pubmed/chemical/Annexin A5,
http://linkedlifedata.com/resource/pubmed/chemical/Dexamethasone,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Prolactin,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0013-7227
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
143
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3060-70
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:12130572-Adrenocorticotropic Hormone,
pubmed-meshheading:12130572-Amino Acid Sequence,
pubmed-meshheading:12130572-Animals,
pubmed-meshheading:12130572-Annexin A1,
pubmed-meshheading:12130572-Annexin A5,
pubmed-meshheading:12130572-Blotting, Western,
pubmed-meshheading:12130572-Dexamethasone,
pubmed-meshheading:12130572-Humans,
pubmed-meshheading:12130572-Male,
pubmed-meshheading:12130572-Molecular Sequence Data,
pubmed-meshheading:12130572-Peptide Fragments,
pubmed-meshheading:12130572-Pituitary Gland, Anterior,
pubmed-meshheading:12130572-Prolactin,
pubmed-meshheading:12130572-Protein Kinase C,
pubmed-meshheading:12130572-Rats,
pubmed-meshheading:12130572-Rats, Sprague-Dawley,
pubmed-meshheading:12130572-Structure-Activity Relationship
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pubmed:year |
2002
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pubmed:articleTitle |
Annexin 1-dependent actions of glucocorticoids in the anterior pituitary gland: roles of the N-terminal domain and protein kinase C.
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pubmed:affiliation |
Department 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.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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