Linked Life Data

18598695

Source:http://linkedlifedata.com/resource/pubmed/id/18598695

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2008-9-1
pubmed:abstractText
Caveolin-1 is an essential structural constituent of caveolae which is involved in regulation of mitogenic signaling and oncogenesis. Caveolin-1 has been implicated in cell migration but its exact role and mechanism of action in this process remained obscure. We have previously reported that expression of caveolin-1 in stably transfected MCF-7 human breast cancer (MCF-7/Cav1) cells up-regulates phosphorylation of a putative Akt substrate protein, designated pp340 [D. Ravid, S. Maor, H. Werner, M. Liscovitch, Caveolin-1 inhibits cell detachment-induced p53 activation and anoikis by upregulation of insulin-like growth factor-I receptors and signaling, Oncogene 24 (2005) 1338-1347.]. We now show, using differential detergent extraction, SDS-PAGE and mass spectrometry, that the major protein in the pp340 band is the actin filament cross-linking protein filamin A. The identity of pp340 as filamin A was confirmed by immunoprecipitation of pp340 with specific filamin A antibodies. RT-PCR, flow cytometry and Western blot analyses show that filamin A mRNA and protein levels are respectively 3.5- and 2.5-fold higher in MCF-7/Cav1 cells than in MCF-7 cells. Basal filamin A phosphorylation on Ser-2152, normalized to total filamin A levels, is 7.8-fold higher in MCF-7/Cav1 than in MCF-7 cells. Insulin-like growth factor-I (IGF-I) stimulates phosphorylation of filamin A on Ser-2152 in MCF-7 cells and further enhances Ser-2152 phosphorylation over its already high basal level in MCF-7/Cav1 cells. The effect of IGF-I is inhibited by the PI3K inhibitor wortmannin, indicating that IGF-I-stimulated phosphorylation of filamin A occurs via the PI3K/Akt pathway. Co-immunoprecipitation experiments have confirmed a previous report showing that filamin A and caveolin-1 co-exist in a complex and have revealed the presence of active phospho-Akt in this complex. Ser-2152 phosphorylation of filamin A has been implicated in cancer cell migration. Accordingly, caveolin-1 expression dramatically enhances IGF-I-dependent MCF-7 cell migration. These data indicate that caveolin-1 specifies filamin A as a novel target for Akt-mediated filamin A Ser-2152 phosphorylation thus mediating the effects of caveolin-1 on IGF-I-induced cancer cell migration.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1090-2422
pubmed:author
pubmed:issnType
Electronic
pubmed:day
10
pubmed:volume
314
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2762-73
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:18598695-Amino Acid Sequence, pubmed-meshheading:18598695-Breast Neoplasms, pubmed-meshheading:18598695-Caveolae, pubmed-meshheading:18598695-Caveolin 1, pubmed-meshheading:18598695-Cell Line, Tumor, pubmed-meshheading:18598695-Cell Membrane, pubmed-meshheading:18598695-Cell Movement, pubmed-meshheading:18598695-Contractile Proteins, pubmed-meshheading:18598695-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:18598695-Humans, pubmed-meshheading:18598695-Insulin-Like Growth Factor I, pubmed-meshheading:18598695-Macromolecular Substances, pubmed-meshheading:18598695-Mass Spectrometry, pubmed-meshheading:18598695-Microfilament Proteins, pubmed-meshheading:18598695-Neoplasm Invasiveness, pubmed-meshheading:18598695-Phosphatidylinositol 3-Kinases, pubmed-meshheading:18598695-Phosphorylation, pubmed-meshheading:18598695-Proto-Oncogene Proteins c-akt, pubmed-meshheading:18598695-RNA, Messenger, pubmed-meshheading:18598695-Serine, pubmed-meshheading:18598695-Signal Transduction, pubmed-meshheading:18598695-Up-Regulation
pubmed:year
2008
pubmed:articleTitle
Filamin A is a novel caveolin-1-dependent target in IGF-I-stimulated cancer cell migration.
pubmed:affiliation
Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't