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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
2009-11-6
pubmed:abstractText
Tissue microenvironment and stroma-derived extracellular matrix (ECM) molecules play important roles in the survival and differentiation of cells. Mouse natural killer (NK) cells usually die within 24 hours once isolated ex vivo. Exogenous cytokines such as interleukin-12 (IL-12) and IL-15 are required to maintain the survival and activity of mouse NK cells cultured in vitro. Whether and how ECM molecules such as fibronectin can support the survival of NK cells remain unknown. We demonstrate that fibronectin, just like IL-15, can maintain survival of mouse NK cells in vitro. Furthermore, we show that fibronectin binds to the CD11b on NK cells, and then CD11b recruits and activates Src. Src can directly interact with beta-catenin and trigger nuclear translocation of beta-catenin. The activation of beta-catenin promotes extracellular signal-related kinase (ERK) phosphorylation, resulting in the increased expression of antiapoptotic protein B-cell leukemia 2 (Bcl-2), which may contribute to the maintenance of NK-cell survival. Consistently, fibronectin cannot maintain the survival of CD11b(-) NK cells and beta-catenin-deficient NK cells in vitro, and the number of NK cells is dramatically decreased in the beta-catenin-deficient mice. Therefore, fibronectin can maintain survival of mouse NK cells by activating ERK and up-regulating Bcl-2 expression via CD11b/Src/beta-catenin pathway.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1528-0020
pubmed:author
pubmed:issnType
Electronic
pubmed:day
5
pubmed:volume
114
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4081-8
pubmed:meshHeading
pubmed-meshheading:19738028-Animals, pubmed-meshheading:19738028-Antigens, CD11b, pubmed-meshheading:19738028-Base Sequence, pubmed-meshheading:19738028-Cell Line, pubmed-meshheading:19738028-Cell Survival, pubmed-meshheading:19738028-DNA Primers, pubmed-meshheading:19738028-Female, pubmed-meshheading:19738028-Fibronectins, pubmed-meshheading:19738028-Humans, pubmed-meshheading:19738028-Killer Cells, Natural, pubmed-meshheading:19738028-MAP Kinase Signaling System, pubmed-meshheading:19738028-Mice, pubmed-meshheading:19738028-Mice, Inbred C57BL, pubmed-meshheading:19738028-Mice, Knockout, pubmed-meshheading:19738028-Mice, Transgenic, pubmed-meshheading:19738028-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:19738028-Signal Transduction, pubmed-meshheading:19738028-beta Catenin, pubmed-meshheading:19738028-src-Family Kinases
pubmed:year
2009
pubmed:articleTitle
Fibronectin maintains survival of mouse natural killer (NK) cells via CD11b/Src/beta-catenin pathway.
pubmed:affiliation
Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, People's Republic of China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't