Linked Life Data

17297451

Source:http://linkedlifedata.com/resource/pubmed/id/17297451

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
33
pubmed:dateCreated
2007-7-19
pubmed:abstractText
Scatter factor (SF) (hepatocyte growth factor) is a pleiotrophic cytokine that accumulates within tumors in vivo and protects tumor cells against cytotoxicity and apoptosis due to DNA damaging agents in vitro. Previous studies have established that SF-mediated cell protection involves antiapoptotic signaling from its receptor (c-Met) to PI3 kinase --> c-Akt --> Pak1 (p21-activated kinase -1) --> NF-kappaB (nuclear factor-kappa B). Here, we found that Ras proteins (H-Ras and R-Ras) enhance SF-mediated activation of NF-kappaB and protection of DU-145 and MDCK (Madin-Darby canine kidney) cells against the topoisomerase IIalpha inhibitor adriamycin. Studies of Ras effector loop mutants and their downstream effectors suggest that Ras/PI3 kinase and Ras/Raf1 pathways contribute to SF stimulation of NF-kappaB signaling and cell protection. Further studies revealed that Raf1 positively regulates the ability of SF to stimulate NF-kappaB activity and cell protection. The ability of Raf1 to stimulate NF-kappaB activity was not due to the classical Raf1 --> MEK1/2 --> ERK1/2 pathway. However, we found that a MEK3/6 --> p38 pathway contributes to SF-mediated activation of NF-kappaB. In contrast, RalA, a target of the Ras/RalGDS pathway negatively regulated the ability of SF to stimulate NF-kappaB activity and cell protection. Ras, Raf1 and RalA modulate SF stimulation of NF-kappaB activity, in part, by regulating IkappaB kinase (IKK)-beta kinase activity. These findings suggest that Ras/Raf1/RalA pathways may converge to modulate NF-kappaB activation and SF-mediated survival signaling at the IKK complex and/or a kinase upstream of this complex.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
19
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4774-96
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17297451-Animals, pubmed-meshheading:17297451-Antibiotics, Antineoplastic, pubmed-meshheading:17297451-Cell Line, pubmed-meshheading:17297451-Cell Line, Tumor, pubmed-meshheading:17297451-Cell Proliferation, pubmed-meshheading:17297451-Cell Survival, pubmed-meshheading:17297451-DNA Damage, pubmed-meshheading:17297451-Dose-Response Relationship, Drug, pubmed-meshheading:17297451-Doxorubicin, pubmed-meshheading:17297451-Genetic Vectors, pubmed-meshheading:17297451-Hepatocyte Growth Factor, pubmed-meshheading:17297451-Humans, pubmed-meshheading:17297451-I-kappa B Kinase, pubmed-meshheading:17297451-Mitogen-Activated Protein Kinases, pubmed-meshheading:17297451-Mutation, pubmed-meshheading:17297451-NF-kappa B, pubmed-meshheading:17297451-Phosphorylation, pubmed-meshheading:17297451-Protein Binding, pubmed-meshheading:17297451-Proto-Oncogene Proteins c-raf, pubmed-meshheading:17297451-RNA Interference, pubmed-meshheading:17297451-Signal Transduction, pubmed-meshheading:17297451-Transfection, pubmed-meshheading:17297451-ral GTP-Binding Proteins, pubmed-meshheading:17297451-ras Proteins
pubmed:year
2007
pubmed:articleTitle
Ras effector pathways modulate scatter factor-stimulated NF-kappaB signaling and protection against DNA damage.
pubmed:affiliation
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057-1469, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural