First Author | Tezuka N | Year | 2007 |
Journal | Biochem Biophys Res Commun | Volume | 356 |
Issue | 3 | Pages | 648-54 |
PubMed ID | 17376403 | Mgi Jnum | J:163129 |
Mgi Id | MGI:4821069 | Doi | 10.1016/j.bbrc.2007.03.019 |
Citation | Tezuka N, et al. (2007) GRB10 binds to LRP6, the Wnt co-receptor and inhibits canonical Wnt signaling pathway. Biochem Biophys Res Commun 356(3):648-54 |
abstractText | Low-density lipoprotein receptor-related protein 6 (LRP6) is a component of cell-surface receptors for Wnt proteins and Wnt is known to promote recruitment of Axin by LRP6 thereby inhibiting beta-catenin's degradation. We show here that growth factor receptor-bound protein10 (GRB10), a multi-modular adaptor protein that is known to associate with several transmembrane tyrosine kinase receptors, binds to the intracellular portion of LRP6 and negatively regulates Wnt signaling. GRB10 overexpression suppressed Wnt3a-, and LRP6-induced but not beta-catenin-induced TCF-dependent-reporter activities in HEK293T cells, suggesting that GRB10 functions upstream of beta-catenin. Actually, GRB10 overexpression attenuated the Wnt3a-induced accumulation of beta-catenin. In addition, RNAi-mediated down-regulation of endogenous GRB10 stimulated Wnt3a-induced reporter activities, indicating that GRB10 is indeed a novel negative regulator of the Wnt signaling pathway. The finding that GRB10 interferes with the binding of Axin to LRP6 indicated a possible molecular mechanism by which the overexpression of GRB10 suppresses Wnt signaling. |