Linked Life Data

20667469

Source:http://linkedlifedata.com/resource/pubmed/id/20667469

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2010-9-14
pubmed:abstractText
Integrin-mediated cell adhesion activates several signaling effectors, including phosphatidylinositol 3-kinase (PI3K), a central mediator of cell motility and survival. To elucidate the molecular mechanisms of this important pathway the specific members of the PI3K family activated by different integrins have to be identified. Here, we studied the role of PI3K catalytic isoforms in ?1 integrin-induced lamellipodium protrusion and activation of Akt in fibroblasts. Real-time total internal reflection fluorescence imaging of the membrane-substrate interface demonstrated that ?1 integrin-mediated attachment induced rapid membrane spreading reaching essentially maximal contact area within 5-10 min. This process required actin polymerization and involved activation of PI3K. Isoform-selective pharmacological inhibition identified p110? as the PI3K catalytic isoform mediating both ?1 integrin-induced cell spreading and Akt phosphorylation. A K756L mutation in the membrane-proximal part of the ?1 integrin subunit, known to cause impaired Akt phosphorylation after integrin stimulation, induced slower cell spreading. The initial ?1 integrin-regulated cell spreading as well as Akt phosphorylation were sensitive to the tyrosine kinase inhibitor PP2, but were not dependent on Src family kinases, FAK or EGF/PDGF receptor transactivation. Notably, cells expressing a Ras binding-deficient p110? mutant were severely defective in integrin-induced Akt phosphorylation, but exhibited identical membrane spreading kinetics as wild-type p110? cells. We conclude that p110? mediates ?1 integrin-regulated activation of Akt and actin polymerization important for survival and lamellipodia dynamics. This could contribute to the tumorigenic properties of cells expressing constitutively active p110?.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1873-3913
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1838-48
pubmed:meshHeading
pubmed-meshheading:20667469-Animals, pubmed-meshheading:20667469-Antigens, CD29, pubmed-meshheading:20667469-Antigens, Polyomavirus Transforming, pubmed-meshheading:20667469-Cell Adhesion, pubmed-meshheading:20667469-Cell Line, Transformed, pubmed-meshheading:20667469-Cell Movement, pubmed-meshheading:20667469-Cell Surface Extensions, pubmed-meshheading:20667469-Cell Transformation, Viral, pubmed-meshheading:20667469-Cell-Matrix Junctions, pubmed-meshheading:20667469-Cells, Cultured, pubmed-meshheading:20667469-Embryo, Mammalian, pubmed-meshheading:20667469-Enzyme Activation, pubmed-meshheading:20667469-Fibroblasts, pubmed-meshheading:20667469-Integrins, pubmed-meshheading:20667469-Isoenzymes, pubmed-meshheading:20667469-Mice, pubmed-meshheading:20667469-Mice, Knockout, pubmed-meshheading:20667469-Phosphatidylinositol 3-Kinases, pubmed-meshheading:20667469-Phosphorylation, pubmed-meshheading:20667469-Proto-Oncogene Proteins c-akt, pubmed-meshheading:20667469-Signal Transduction, pubmed-meshheading:20667469-src-Family Kinases
pubmed:year
2010
pubmed:articleTitle
PI3-kinase p110? mediates ?1 integrin-induced Akt activation and membrane protrusion during cell attachment and initial spreading.
pubmed:affiliation
Department of Medical Biochemistry and Microbiology, Uppsala University, SE-751 23 Uppsala, Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't