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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
27
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pubmed:dateCreated |
2001-7-2
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pubmed:abstractText |
Activation of Ras signaling by growth factors has been associated with gene regulation and cell proliferation. Here we characterize the contributory role of cytosolic phospholipase A(2) in the oncogenic Ha-Ras(V12) signaling pathway leading to activation of c-fos serum response element (SRE) and transformation in Rat-2 fibroblasts. Using a c-fos SRE-luciferase reporter gene, we showed that the transactivation of SRE by Ha-Ras(V12) is mainly via a Rac-linked cascade, although the Raf-mitogen-activated protein kinase cascade is required for full activation. In addition, Ha-Ras(V12)-induced DNA synthesis was significantly attenuated by microinjection of recombinant Rac(N17), a dominant negative mutant of Rac1. To identify the mediators downstream of Rac in the Ha-Ras(V12) signaling, we investigated the involvement of cytosolic phospholipase A(2). Oncogenic Ha-Ras(V12)-induced SRE activation was significantly inhibited by either pretreatment with mepacrine, a phospholipase A(2) inhibitor, or cotransfection with the antisense oligonucleotide of cytosolic phospholipase A(2). We also found cytosolic phospholipase A(2) to be situated downstream of Ha-Ras(V12) in a signal pathway leading to transformation. Together, these results are indicative of mediatory roles of Rac and cytosolic phospholipase A(2) in the signaling pathway by which Ha-Ras(V12) transactivates c-fos SRE and transformation. Our findings point to cytosolic phospholipase A(2) as a novel potential target for suppressing oncogenic Ha-Ras(V12) signaling in the cell.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oligonucleotides, Antisense,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipases A,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipases A2,
http://linkedlifedata.com/resource/pubmed/chemical/Quinacrine,
http://linkedlifedata.com/resource/pubmed/chemical/Serum Response Factor,
http://linkedlifedata.com/resource/pubmed/chemical/rac1 GTP-Binding Protein,
http://linkedlifedata.com/resource/pubmed/chemical/ras Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
6
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pubmed:volume |
276
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
24645-53
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:11323430-Animals,
pubmed-meshheading:11323430-Base Sequence,
pubmed-meshheading:11323430-DNA Replication,
pubmed-meshheading:11323430-DNA-Binding Proteins,
pubmed-meshheading:11323430-Fibroblasts,
pubmed-meshheading:11323430-Genes, Reporter,
pubmed-meshheading:11323430-Genes, ras,
pubmed-meshheading:11323430-Luciferases,
pubmed-meshheading:11323430-Microinjections,
pubmed-meshheading:11323430-Molecular Sequence Data,
pubmed-meshheading:11323430-Nuclear Proteins,
pubmed-meshheading:11323430-Oligonucleotides, Antisense,
pubmed-meshheading:11323430-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:11323430-Phospholipases A,
pubmed-meshheading:11323430-Phospholipases A2,
pubmed-meshheading:11323430-Quinacrine,
pubmed-meshheading:11323430-Rats,
pubmed-meshheading:11323430-Serum Response Factor,
pubmed-meshheading:11323430-Signal Transduction,
pubmed-meshheading:11323430-Transcriptional Activation,
pubmed-meshheading:11323430-Transfection,
pubmed-meshheading:11323430-rac1 GTP-Binding Protein,
pubmed-meshheading:11323430-ras Proteins
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pubmed:year |
2001
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pubmed:articleTitle |
Role of the cytosolic phospholipase A2-linked cascade in signaling by an oncogenic, constitutively active Ha-Ras isoform.
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pubmed:affiliation |
Department of Life Science, Kwangju Institute of Science and Technology, Kwang-Ju 500-712, Korea.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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