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Role of HGF phosphorylation of beta‐catenin at Y654 in embryonic mouse liver development
Author(s) -
Lade Abigale,
Monga Satdarshan Pal
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.998.4
Subject(s) - biology , wnt signaling pathway , phosphorylation , microbiology and biotechnology , beta catenin , tyrosine phosphorylation , knockout mouse , embryonic stem cell , gene knockout , hepatocyte growth factor , cell growth , signal transduction , endocrinology , medicine , receptor , gene , genetics
Beta‐catenin is the effector of the Wnt signaling pathway, a pathway involved in diverse cellular functions including regulation of proliferation, survival, adhesion, and differentiation. Phosphorylation of beta‐catenin at residue Y654 by one of several receptor tyrosine kinases inhibits its association with E‐cadherin at the cell membrane, destabilizing cell‐cell adhesions. We have found high levels of phosphorylation of Y654 during liver bud expansion between E12.5 and E14.5 in embryonic mice, suggesting a role for the phosphorylation of this residue in promoting liver growth. Furthermore, we have found c‐Met to be expressed and active in mouse liver at these stages. Intriguingly, previous work has revealed that c‐Met knock‐out mice die at late gestation, at approximately the same stage at which lethality occurs in hepatoblast‐specific beta‐catenin knock‐out mice. Both knockouts exhibit decreased parenchymal cell mass and reduced liver size, as well as increased hepatocyte apoptosis. In addition, while tail vein injection of a naked DNA plasmid encoding HGF promotes hepatomegaly, this effect is not seen in beta‐catenin knockout mice. Together, our results suggest that Met promotes liver growth by phosphorylating membrane beta‐catenin at residue Y654 to promote its nuclear translocation and activation of target genes, and that this event is essential for liver development in mice.