Linked Life Data

11713255

Source:http://linkedlifedata.com/resource/pubmed/id/11713255

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2002-2-11
pubmed:abstractText
The signaling pathways that mediate the transforming activity of the Rac1 GTPase remain to be determined. In the present study, we used effector domain mutants of the constitutively activated Rac(61L) mutant that display differential transforming activities and differential activation of downstream effector pathways to investigate the contribution of p70 S6 kinase (p70(S6K)) to Rac1 transformation and to decipher the signaling pathways leading from Rac1 to p70(S6K). First, we found that Rac1 transforming activity could be dissociated from Rac1 activation of p70(S6K). A weakly transforming Rac1 mutant retained the ability to activate p70(S6K), whereas some potently transforming effector mutants were impaired in their ability to activate p70(S6K). These data suggest that p70(S6K) is not necessary to promote full Rac1 transforming activity. We also found a strong correlation between the ability of the Rac(61L) effector mutants to activate p70(S6K) and their ability to activate the JNK mitogen-activated protein kinase. We found that the MLK3 serine/threonine kinase activated JNK and p70(S6K), whereas activation of p70(S6K) by Rac(61L) was significantly inhibited by dominant-negative MLK3. Additionally, the ability of the Rac(61L) effector mutants to activate MLK3 correlated well with their ability to activate p70(S6K) and JNK. Taken together, these results provide evidence that Rac1 coordinately activates p70(S6K) and JNK via MLK3 activation. Finally, we found that co-expression of wild type, but not kinase-dead, MLK3 significantly inhibited Rac1 transforming activity. These results suggest that MLK3 may be a negative regulator of the growth-promoting and transforming properties of Rac1.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
277
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4770-7
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:11713255-3T3 Cells, pubmed-meshheading:11713255-Agar, pubmed-meshheading:11713255-Animals, pubmed-meshheading:11713255-Blotting, Western, pubmed-meshheading:11713255-Cell Line, pubmed-meshheading:11713255-Enzyme Activation, pubmed-meshheading:11713255-Genes, Reporter, pubmed-meshheading:11713255-Genetic Vectors, pubmed-meshheading:11713255-Humans, pubmed-meshheading:11713255-Luciferases, pubmed-meshheading:11713255-MAP Kinase Kinase Kinases, pubmed-meshheading:11713255-Mice, pubmed-meshheading:11713255-Mitogen-Activated Protein Kinase 8, pubmed-meshheading:11713255-Mitogen-Activated Protein Kinases, pubmed-meshheading:11713255-Mutation, pubmed-meshheading:11713255-Plasmids, pubmed-meshheading:11713255-Precipitin Tests, pubmed-meshheading:11713255-Protein Binding, pubmed-meshheading:11713255-Protein Structure, Tertiary, pubmed-meshheading:11713255-Ribosomal Protein S6 Kinases, pubmed-meshheading:11713255-Signal Transduction, pubmed-meshheading:11713255-Transfection, pubmed-meshheading:11713255-rac1 GTP-Binding Protein
pubmed:year
2002
pubmed:articleTitle
Role of MLK3-mediated activation of p70 S6 kinase in Rac1 transformation.
pubmed:affiliation
Lineberger Comprehensive Cancer Center, Department of Pharmacology and Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina 27599-7295, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.