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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
51
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pubmed:dateCreated |
2002-12-16
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pubmed:abstractText |
Fibroblast growth factor homologous factors (FHFs) form native intracellular complexes with the mitogen-activated protein kinase (MAPK) scaffold protein islet-brain 2 (IB2) in adult brain. FHF binding to IB2 facilitates recruitment of the MAPK p38delta (SAPK4), while failing to stimulate binding of JNK, the preferred kinase of the related scaffold IB1 (JIP-1). We now report further biochemical evidence supporting FHFs as regulators of IB2 scaffold activity. Mixed lineage kinase 3 (MLK3) and IB2 synergistically activate p38delta but not the MAPKs JNK-1 and p38alpha. Binding of p38delta to IB2 is mediated by the carboxyl-terminal half of the scaffold (IB2(Delta1-436)). FHF2 also binds weakly to IB2(Delta1-436) and can thereby increase p38delta interaction with IB2(Delta1-436). FHF-induced recruitment of p38delta to IB2 is accompanied by increased levels of activated p38delta, and synergistic activation of p38delta by MLK3 and IB2 is further enhanced by FHF2. Consistent with a role for FHFs as signaling molecules, FHF2 isolated from rat brain is serine/threonine-phosphorylated, and FHF can serve as a substrate for p38delta in vitro. These results support the existence of a signaling module in which IB2 scaffolds a MLK3/MKK/p38delta kinase cascade. FHFs aid in recruitment of p38 to IB2 and may serve as kinase substrates.
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/MAPK8IP1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/MAPK8IP2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Mapk8ip protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Mapk8ip protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Mapk8ip2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 13,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 14,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/mitogen-activated protein kinase...,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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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 |
20
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pubmed:volume |
277
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
49111-9
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pubmed:dateRevised |
2010-12-3
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pubmed:meshHeading |
pubmed-meshheading:12244047-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:12244047-Alternative Splicing,
pubmed-meshheading:12244047-Animals,
pubmed-meshheading:12244047-Binding Sites,
pubmed-meshheading:12244047-Blotting, Western,
pubmed-meshheading:12244047-Brain,
pubmed-meshheading:12244047-Carrier Proteins,
pubmed-meshheading:12244047-Cell Line,
pubmed-meshheading:12244047-Cerebellum,
pubmed-meshheading:12244047-Cerebral Cortex,
pubmed-meshheading:12244047-Enzyme Activation,
pubmed-meshheading:12244047-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:12244047-Genetic Vectors,
pubmed-meshheading:12244047-Humans,
pubmed-meshheading:12244047-MAP Kinase Kinase Kinases,
pubmed-meshheading:12244047-MAP Kinase Signaling System,
pubmed-meshheading:12244047-Mice,
pubmed-meshheading:12244047-Mitogen-Activated Protein Kinase 13,
pubmed-meshheading:12244047-Mitogen-Activated Protein Kinase 14,
pubmed-meshheading:12244047-Mitogen-Activated Protein Kinases,
pubmed-meshheading:12244047-Models, Genetic,
pubmed-meshheading:12244047-Phosphorylation,
pubmed-meshheading:12244047-Precipitin Tests,
pubmed-meshheading:12244047-Protein Binding,
pubmed-meshheading:12244047-Protein Structure, Tertiary,
pubmed-meshheading:12244047-Rats,
pubmed-meshheading:12244047-Signal Transduction,
pubmed-meshheading:12244047-Substrate Specificity,
pubmed-meshheading:12244047-Transfection,
pubmed-meshheading:12244047-p38 Mitogen-Activated Protein Kinases
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pubmed:year |
2002
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pubmed:articleTitle |
Fibroblast growth factor homologous factors and the islet brain-2 scaffold protein regulate activation of a stress-activated protein kinase.
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pubmed:affiliation |
Department of Molecular, Cell and Developmental Biology, Mount Sinai School of Medicine, 1 Gustave Levy Place, New York, NY 10029, USA.
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pubmed:publicationType |
Journal Article
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