Linked Life Data

19596799

Source:http://linkedlifedata.com/resource/pubmed/id/19596799

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 15
pubmed:dateCreated
2009-7-23
pubmed:abstractText
During the development of pressure-induced cardiac hypertrophy, fibroblasts are activated to become myofibroblasts, which exhibit actin-cytoskeletal remodeling and express alpha-smooth muscle actin (SMA; encoded by ACTA2). Currently, the mechanosensing signaling pathways that regulate SMA expression are not defined. Because focal-adhesion complexes are putative mechanosensing organelles, we examined the role of focal adhesion kinase (FAK) and its interaction with gelsolin in the regulation of SMA expression. We subjected NIH3T3 cells to tensile forces (0.65 pN/mum(2)) by using collagen-coated magnetite beads attached to integrins. After stimulation by mechanical force, FAK and gelsolin were recruited to magnetite beads and there was increased phosphorylation of Tyr397FAK. Mechanical force enhanced SMA promoter activity by twofold; this increased activity was blocked by FAK knockdown using siRNA and by deletion of gelsolin. Force-induced nuclear translocation of MRTF-A, a transcriptional co-activator of SMA that is regulated by actin filaments, was also reduced by FAK knockdown. Phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P(2)], which uncaps gelsolin from actin filaments, was enriched at sites of force application. Type-I phosphatidylinositol 4-phosphate 5 kinase-gamma (PIP5KIgamma), which generates PtdIns(4,5)P(2), associated with FAK and was required for force-mediated SMA-promoter activity and actin assembly. Catalytically inactive PIP5KIgamma inhibited force-induced phosphorylation of FAK at Tyr397. These data suggest a novel pathway in which mechanosensing by FAK regulates actin assembly via gelsolin and the activity of PIP5KIgamma; actin assembly in turn controls SMA expression via MRTF-A.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/1-phosphatidylinositol-4-phosphate..., http://linkedlifedata.com/resource/pubmed/chemical/Actins, http://linkedlifedata.com/resource/pubmed/chemical/Focal Adhesion Kinase 1, http://linkedlifedata.com/resource/pubmed/chemical/Gelsolin, http://linkedlifedata.com/resource/pubmed/chemical/MKL1 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol Phosphates, http://linkedlifedata.com/resource/pubmed/chemical/Phosphotransferases (Alcohol Group..., http://linkedlifedata.com/resource/pubmed/chemical/Ptk2 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering, http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators, http://linkedlifedata.com/resource/pubmed/chemical/alpha-smooth muscle actin, mouse, http://linkedlifedata.com/resource/pubmed/chemical/phosphatidylinositol 4-phosphate
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0021-9533
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
122
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2769-81
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
FAK, PIP5KIgamma and gelsolin cooperatively mediate force-induced expression of alpha-smooth muscle actin.
pubmed:affiliation
CIHR Group in Matrix Dynamics, University of Toronto, Toronto, Ontario, Canada M5S 3E2. matthew.chan@utoronto.ca
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't