Linked Life Data

21454615

Source:http://linkedlifedata.com/resource/pubmed/id/21454615

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
2011-5-16
pubmed:abstractText
TGF-? modulates numerous diverse cellular phenotypes including growth arrest in epithelial cells and proliferation in fibroblasts. Although the Smad pathway is fundamental for the majority of these responses, recent evidence indicates that non-Smad pathways may also have a critical role. Here we report a novel mechanism whereby the nonreceptor tyrosine focal adhesion kinase (FAK) functions as an adaptor necessary for cell type-specific responses to TGF-?. We show that in contrast to Smad actions, non-Smad pathways, including c-Abl, PAK2, and Akt, display an obligate requirement for FAK. Interestingly, this occurs in Src null SYF cells and is independent of FAK tyrosine phosphorylation, kinase activity, and/or proline-rich sequences in the C-terminal FAT domain. FAK binds the phosphatidylinositol 3-kinase (PI3K) p85 regulatory subunit following TGF-? treatment in a subset of fibroblasts but not epithelial cells and has an obligate role in TGF-?-stimulated anchorage-independent growth and migration. Together, these results uncover a new scaffolding role for FAK as the most upstream component regulating the profibrogenic action of TGF-? and suggest that inhibiting this interaction may be useful in treating a number of fibrotic diseases.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1083-351X
pubmed:author
pubmed:copyrightInfo
© 2011 by The American Society for Biochemistry and Molecular Biology, Inc.
pubmed:issnType
Electronic
pubmed:day
20
pubmed:volume
286
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
17841-50
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Non-Smad transforming growth factor-? signaling regulated by focal adhesion kinase binding the p85 subunit of phosphatidylinositol 3-kinase.
pubmed:affiliation
Department of Biochemistry/Molecular Biology and Medicine, Thoracic Diseases Research Unit, Mayo Clinic Cancer Center, Mayo Clinic, Rochester, Minnesota 55905, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural