| http://purl.uniprot.org/citations/15731459 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/15731459 | http://www.w3.org/2000/01/rdf-schema#comment | "Mechanotransduction represents an integral part of vascular homeostasis and contributes to vascular lesion formation. Previously, we demonstrated a mechanosensitive activation of phosphoinositide 3-kinase (PI3-K)/protein kinase B (Akt) resulting in p27Kip1 transcriptional downregulation and cell cycle entry of vascular smooth muscle cells (VSMC). In this study, we further elucidated the signaling from outside-in toward PI3-K/Akt in vitro and in an in vivo model of elevated tensile force. When VSMC were subjected to cyclic stretch (0.5 Hz at 125% resting length), PI3-K, Akt, and Src kinases were found activated. Disrupting caveolar structures with beta-cyclodextrin or transfection of VSMC with caveolin-1 antisense oligonucleotides (ODN) prevented PI3-K and Akt activation and cell cycle entry. Furthermore, PI3-K and Akt were resistant to activation when Src kinases were inhibited pharmacologically or by overexpression of a kinase-dead c-Src mutant. alpha(V)beta3 integrins were identified to colocalize with PI3-K/caveolin-1 complexes, and blockade of alpha(V)beta3 integrins prevented Akt activation. The central role of caveolin-1 in mechanotransduction was further examined in an in vivo model of elevated tensile force. Interposition of wild-type (WT) jugular veins into WT carotid arteries resulted in a rapid Akt activation within the veins that was almost abolished when veins of caveolin-1 knockout (KO) mice were used. Furthermore, late neointima formation within the KO veins was significantly reduced. Our study provides evidence that PI3-K/Akt is critically involved in mechanotransduction of VSMC in vitro and within the vasculature in vivo. Furthermore, caveolin-1 is essential for the integrin-mediated activation of PI3-K/Akt."xsd:string |
| http://purl.uniprot.org/citations/15731459 | http://purl.org/dc/terms/identifier | "doi:10.1161/01.res.0000160610.61306.0f"xsd:string |
| http://purl.uniprot.org/citations/15731459 | http://purl.uniprot.org/core/author | "Kummer W."xsd:string |
| http://purl.uniprot.org/citations/15731459 | http://purl.uniprot.org/core/author | "Eickelberg O."xsd:string |
| http://purl.uniprot.org/citations/15731459 | http://purl.uniprot.org/core/author | "Braun-Dullaeus R.C."xsd:string |
| http://purl.uniprot.org/citations/15731459 | http://purl.uniprot.org/core/author | "Strasser R.H."xsd:string |
| http://purl.uniprot.org/citations/15731459 | http://purl.uniprot.org/core/author | "Sedding D.G."xsd:string |
| http://purl.uniprot.org/citations/15731459 | http://purl.uniprot.org/core/author | "Tillmanns H."xsd:string |
| http://purl.uniprot.org/citations/15731459 | http://purl.uniprot.org/core/author | "Hermsen J."xsd:string |
| http://purl.uniprot.org/citations/15731459 | http://purl.uniprot.org/core/author | "Schwencke C."xsd:string |
| http://purl.uniprot.org/citations/15731459 | http://purl.uniprot.org/core/author | "Seay U."xsd:string |
| http://purl.uniprot.org/citations/15731459 | http://purl.uniprot.org/core/date | "2005"xsd:gYear |
| http://purl.uniprot.org/citations/15731459 | http://purl.uniprot.org/core/name | "Circ Res"xsd:string |
| http://purl.uniprot.org/citations/15731459 | http://purl.uniprot.org/core/pages | "635-642"xsd:string |
| http://purl.uniprot.org/citations/15731459 | http://purl.uniprot.org/core/title | "Caveolin-1 facilitates mechanosensitive protein kinase B (Akt) signaling in vitro and in vivo."xsd:string |
| http://purl.uniprot.org/citations/15731459 | http://purl.uniprot.org/core/volume | "96"xsd:string |
| http://purl.uniprot.org/citations/15731459 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/15731459 |
| http://purl.uniprot.org/citations/15731459 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/15731459 |
| http://purl.uniprot.org/uniprot/P41350#attribution-C2C37A1786A69FDD77D1E2520EDCD24A | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/15731459 |
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