Linked Life Data

12639897

Source:http://linkedlifedata.com/resource/pubmed/id/12639897

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2003-3-17
pubmed:abstractText
Our recent studies on rat pituitary tissue suggest that the annexin 1 (ANXA1)-dependent inhibitory actions of glucocorticoids on ACTH secretion are effected via a paracrine mechanism that involves protein kinase C (PKC)-dependent translocation of a serine-phosphorylated species of ANXA1 (Ser-P-ANXA1) to the plasma membrane of the nonsecretory folliculostellate cells. In the present study, we have used a human folliculostellate cell line (PDFS) to explore the signaling mechanisms that cause the translocation of Ser-P-ANXA1 to the membrane together with Western blot analysis and flow cytometry to detect the phosphorylated protein. Exposure of PDFS cells to dexamethasone caused time-dependent increases in the expression of ANXA1 mRNA and protein, which were first detected within 2 h of steroid contact. This genomic response was preceded by the appearance within 30 min of substantially increased amounts of Ser-P-ANXA1 and by translocation of the phosphorylated protein to the cell surface. The prompt membrane translocation of Ser-P-ANXA1 provoked by dexamethasone was inhibited by the glucocorticoid receptor, antagonist, mifepristone, but not by actinomycin D or cycloheximide, which effectively inhibit mRNA and protein synthesis respectively in our preparation. It was also inhibited by a nonselective PKC inhibitor (PKC(9-31)), by a selective inhibitor of Ca(2+)-dependent PKCs (Go 6976) and by annexin 5 (which sequesters PKC in other systems). In addition, blockade of phosphatidylinositiol 3-kinase (wortmannin) or MAPK pathways with PD 98059 or UO 126 (selective for MAPK kinse 1 and 2) prevented the steroid-induced translocation of Ser-P-ANXA1 to the cell surface. These results suggest that glucocorticoids induce rapid serine phosphorylation and membrane translocation of ANXA1 via a novel nongenomic, glucocorticoid receptor-dependent mechanism that requires MAPK, phosphatidylinositiol 3-kinase, and Ca(2+)-dependent PKC pathways.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
144
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1164-74
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:12639897-Adenocarcinoma, Follicular, pubmed-meshheading:12639897-Animals, pubmed-meshheading:12639897-Annexin A1, pubmed-meshheading:12639897-Cell Membrane, pubmed-meshheading:12639897-Dexamethasone, pubmed-meshheading:12639897-Enzyme Inhibitors, pubmed-meshheading:12639897-Gene Expression, pubmed-meshheading:12639897-Glucocorticoids, pubmed-meshheading:12639897-Humans, pubmed-meshheading:12639897-MAP Kinase Signaling System, pubmed-meshheading:12639897-Mitogen-Activated Protein Kinases, pubmed-meshheading:12639897-Phosphatidylinositol 3-Kinases, pubmed-meshheading:12639897-Phosphorylation, pubmed-meshheading:12639897-Pituitary Neoplasms, pubmed-meshheading:12639897-Protein Kinase C, pubmed-meshheading:12639897-Rabbits, pubmed-meshheading:12639897-Receptors, Glucocorticoid, pubmed-meshheading:12639897-Serine, pubmed-meshheading:12639897-Tumor Cells, Cultured
pubmed:year
2003
pubmed:articleTitle
Dexamethasone induces rapid serine-phosphorylation and membrane translocation of annexin 1 in a human folliculostellate cell line via a novel nongenomic mechanism involving the glucocorticoid receptor, protein kinase C, phosphatidylinositol 3-kinase, and mitogen-activated protein kinase.
pubmed:affiliation
Department of Neuroendocrinology, Division of Neuroscience and Psychological Medicine, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London W12 ONN, United Kingdom. e.solito@imperial.ac.uk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't