Xenbase is experiencing difficulties due to technical problems with the University of Calgary IT infrastructure and may go temporarily offline.

Click on this message to dismiss it.
Click here to close Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly. We suggest using a current version of Chrome, FireFox, or Safari.
XB-ART-38158
Nature. July 17, 2008; 454 (7202): 345-9.

IGFBP-4 is an inhibitor of canonical Wnt signalling required for cardiogenesis.

Zhu W , Shiojima I , Ito Y , Li Z , Ikeda H , Yoshida M , Naito AT , Nishi J , Ueno H , Umezawa A , Minamino T , Nagai T , Kikuchi A , Asashima M , Komuro I .


Abstract
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.

PubMed ID: 18528331
Article link: Nature.

Genes referenced: fzd8 gata4 hhex igfbp1 igfbp2 igfbp4 igfbp5 il17f ins lrp6 mhc1a myc myh6 nkx2-5 nodal3.1 sia1 tnni3 wnt3a
Morpholinos referenced: Igfbp4 MO1 Igfbp4 MO2

Article Images: [+] show captions

My Xenbase: [ Log-in / Register ]
version: [3.11.2]

Major funding for Xenbase is provided by the National Institute of Child Health and Human Development, grant P41 HD064556