Downregulation of Akt activity contributes to the growth arrest induced by FGF in chondrocytes

Journal of Cellular Physiology
Riccardo PrioreClaudio Basilico

Abstract

Unregulated FGF signaling produced by activating FGFR3 mutations causes several forms of dwarfism-associated chondrodysplasias in humans and mice. FGF signaling inhibits chondrocyte proliferation by activating multiple signal transduction pathways that all contribute to chondrocyte growth arrest and induction of some aspects of differentiation. Previous studies had identified the Stat1 pathway, dephosphorylation of the Rb family proteins p107 and p130, induction of p21 expression and sustained activation of MAP kinases as playing a role in the FGF response of chondrocytes. We have examined the role of Akt (PKB) in the response of chondrocytes to FGF signaling. Differently from what is observed in many other cell types, FGF does not activate Akt in chondrocytes, and Akt phosphorylation is actually downregulated after FGF treatment. By expressing a constitutively activated, myristylated form of Akt (myr-Akt) in the RCS chondrosarcoma cell line, we show that Akt activation partially counteracts the inhibitory effect of FGF signaling. The response of myr-Akt expressing cells to FGF is identical to parental RCS in the first few hours after treatment, but then diverges as myr-Akt cells show decreased p130 phosphorylation, increased c...Continue Reading

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Citations

Nov 20, 2013·PLoS Computational Biology·Luca GriecoDenis Thieffry
Apr 18, 2014·Journal of Molecular Endocrinology·Julian C LuiJeffrey Baron
May 16, 2014·Journal of Signal Transduction·Rajesh RajuHarsha Gowda
Sep 11, 2008·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Keisuke KitaToru Nakano
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Mar 12, 2008·The Journal of Biological Chemistry·Gary J LitherlandAndrew D Rowan
Jan 17, 2008·Journal of Cell Science·Pavel KrejciWilliam R Wilcox
Jul 30, 2015·Genes & Development·David M Ornitz, Pierre J Marie

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