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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
37
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pubmed:dateCreated |
2004-9-6
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pubmed:abstractText |
Sef was recently identified as a negative regulator of fibroblast growth factor (FGF) signaling in a genetic screen of zebrafish and subsequently in mouse and humans. By inhibiting FGFR1 tyrosine phosphorylation and/or Ras downstream events, Sef inhibits FGF-mediated ERK activation and cell proliferation as well as PC12 cell differentiation. Here we show that Sef and a deletion mutant of Sef lacking the extracellular domain (SefIC) physically interact with TAK1 (transforming growth factor-beta-associated kinase) and activate JNK through a TAK1-MKK4-JNK pathway. Sef and SefIC overexpression also resulted in apoptotic cell death, while dominant negative forms of MKK4 and TAK1 blocked Sef-mediated JNK activation and attendant 293T cell apoptosis. These investigations reveal a novel activating function of Sef that is distinct from its inhibitory effect on FGF receptor signaling and ERK activation.
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pubmed:grant |
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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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 |
10
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
38099-102
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:15277532-Animals,
pubmed-meshheading:15277532-Apoptosis,
pubmed-meshheading:15277532-Cell Differentiation,
pubmed-meshheading:15277532-Cell Division,
pubmed-meshheading:15277532-Cell Line,
pubmed-meshheading:15277532-Dose-Response Relationship, Drug,
pubmed-meshheading:15277532-Enzyme Activation,
pubmed-meshheading:15277532-Flow Cytometry,
pubmed-meshheading:15277532-Gene Deletion,
pubmed-meshheading:15277532-Genes, Dominant,
pubmed-meshheading:15277532-Humans,
pubmed-meshheading:15277532-Immunoblotting,
pubmed-meshheading:15277532-JNK Mitogen-Activated Protein Kinases,
pubmed-meshheading:15277532-MAP Kinase Kinase 4,
pubmed-meshheading:15277532-MAP Kinase Kinase Kinases,
pubmed-meshheading:15277532-Microscopy, Fluorescence,
pubmed-meshheading:15277532-Mitogen-Activated Protein Kinase Kinases,
pubmed-meshheading:15277532-Mitogen-Activated Protein Kinases,
pubmed-meshheading:15277532-Mutation,
pubmed-meshheading:15277532-PC12 Cells,
pubmed-meshheading:15277532-Phosphorylation,
pubmed-meshheading:15277532-Plasmids,
pubmed-meshheading:15277532-Precipitin Tests,
pubmed-meshheading:15277532-Protein Binding,
pubmed-meshheading:15277532-Rats,
pubmed-meshheading:15277532-Receptors, Interleukin,
pubmed-meshheading:15277532-Signal Transduction,
pubmed-meshheading:15277532-Time Factors,
pubmed-meshheading:15277532-Transfection,
pubmed-meshheading:15277532-Xenopus
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pubmed:year |
2004
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pubmed:articleTitle |
Sef interacts with TAK1 and mediates JNK activation and apoptosis.
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pubmed:affiliation |
Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, Maine 04074, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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