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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7202
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pubmed:dateCreated |
2008-7-17
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pubmed:abstractText |
Insulin-like growth-factor-binding proteins (IGFBPs) bind to and modulate the actions of insulin-like growth factors (IGFs). Although some of the actions of IGFBPs have been reported to be independent of IGFs, the precise mechanisms of IGF-independent actions of IGFBPs are largely unknown. Here we report a previously unknown function for IGFBP-4 as a cardiogenic growth factor. IGFBP-4 enhanced cardiomyocyte differentiation in vitro, and knockdown of Igfbp4 attenuated cardiomyogenesis both in vitro and in vivo. The cardiogenic effect of IGFBP-4 was independent of its IGF-binding activity but was mediated by the inhibitory effect on canonical Wnt signalling. IGFBP-4 physically interacted with a Wnt receptor, Frizzled 8 (Frz8), and a Wnt co-receptor, low-density lipoprotein receptor-related protein 6 (LRP6), and inhibited the binding of Wnt3A to Frz8 and LRP6. Although IGF-independent, the cardiogenic effect of IGFBP-4 was attenuated by IGFs through IGFBP-4 sequestration. IGFBP-4 is therefore an inhibitor of the canonical Wnt signalling required for cardiogenesis and provides a molecular link between IGF signalling and Wnt signalling.
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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/Insulin-Like Growth Factor Binding...,
http://linkedlifedata.com/resource/pubmed/chemical/LDL-Receptor Related Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Low Density Lipoprotein...,
http://linkedlifedata.com/resource/pubmed/chemical/Lrp6 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, G-Protein-Coupled,
http://linkedlifedata.com/resource/pubmed/chemical/Somatomedins,
http://linkedlifedata.com/resource/pubmed/chemical/Wnt Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Wnt-3a protein, Xenopus,
http://linkedlifedata.com/resource/pubmed/chemical/Wnt3 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Wnt3A Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Wnt3a protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Xenopus Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin,
http://linkedlifedata.com/resource/pubmed/chemical/frizzled 8 protein, mouse
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1476-4687
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pubmed:author |
pubmed-author:AsashimaMakotoM,
pubmed-author:IkedaHiroyukiH,
pubmed-author:ItoYuzuruY,
pubmed-author:KikuchiAkiraA,
pubmed-author:KomuroIsseiI,
pubmed-author:LiZhiZ,
pubmed-author:MinaminoTohruT,
pubmed-author:NagaiToshioT,
pubmed-author:NaitoAtsuhiko TAT,
pubmed-author:NishiJun-ichiroJ,
pubmed-author:ShiojimaIchiroI,
pubmed-author:UenoHirooH,
pubmed-author:UmezawaAkihiroA,
pubmed-author:YoshidaMasashiM,
pubmed-author:ZhuWeidongW
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pubmed:issnType |
Electronic
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pubmed:day |
17
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pubmed:volume |
454
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
345-9
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:18528331-Animals,
pubmed-meshheading:18528331-Cell Differentiation,
pubmed-meshheading:18528331-Cell Line, Tumor,
pubmed-meshheading:18528331-Embryo, Nonmammalian,
pubmed-meshheading:18528331-Heart,
pubmed-meshheading:18528331-Insulin-Like Growth Factor Binding Protein 4,
pubmed-meshheading:18528331-LDL-Receptor Related Proteins,
pubmed-meshheading:18528331-Low Density Lipoprotein Receptor-Related Protein-6,
pubmed-meshheading:18528331-Mice,
pubmed-meshheading:18528331-Myocytes, Cardiac,
pubmed-meshheading:18528331-Receptors, G-Protein-Coupled,
pubmed-meshheading:18528331-Signal Transduction,
pubmed-meshheading:18528331-Somatomedins,
pubmed-meshheading:18528331-Wnt Proteins,
pubmed-meshheading:18528331-Wnt3 Protein,
pubmed-meshheading:18528331-Wnt3A Protein,
pubmed-meshheading:18528331-Xenopus Proteins,
pubmed-meshheading:18528331-Xenopus laevis,
pubmed-meshheading:18528331-beta Catenin
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pubmed:year |
2008
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pubmed:articleTitle |
IGFBP-4 is an inhibitor of canonical Wnt signalling required for cardiogenesis.
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pubmed:affiliation |
Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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