The kinase activity of the FGFR3 mutant (TDII-FGFR3) hampers its maturation: as a consequence the immature receptor activates ERKs from the endoplasmic reticulum (ER), hence apoptosis. Differently, in stable TDII-FGFR3 cells, receptor biosynthesis is restored and ERKs are activated from cell surface. To identify potential mediators of cell adaptation to the activated receptor we investigated on gene products differently regulated in TDII versus wild type FGFR3 cells. cDNA representational difference analysis reveals Sprouty4 up regulation in the TDII-FGFR3 cells. Furthermore, Sprouty4 inhibits the TDII-FGFR3-mediated ERKs activation from the ER but fails to suppress ERKs activation from cell surface. We conclude that cell adaptation to activated FGFR3 include Sprouty4 activity to silence the premature receptor signaling and suppress apoptosis.

Cell adaptation to activated FGFR3 includes Sprouty4 up regulation to inhibit the receptor-mediated ERKs activation from the endoplasmic reticulum

LIEVENS, Patricia;LIBOI, Elio Maria
2009

Abstract

The kinase activity of the FGFR3 mutant (TDII-FGFR3) hampers its maturation: as a consequence the immature receptor activates ERKs from the endoplasmic reticulum (ER), hence apoptosis. Differently, in stable TDII-FGFR3 cells, receptor biosynthesis is restored and ERKs are activated from cell surface. To identify potential mediators of cell adaptation to the activated receptor we investigated on gene products differently regulated in TDII versus wild type FGFR3 cells. cDNA representational difference analysis reveals Sprouty4 up regulation in the TDII-FGFR3 cells. Furthermore, Sprouty4 inhibits the TDII-FGFR3-mediated ERKs activation from the ER but fails to suppress ERKs activation from cell surface. We conclude that cell adaptation to activated FGFR3 include Sprouty4 activity to silence the premature receptor signaling and suppress apoptosis.
FGFR3; endoplasmic reticulum; Erk1/2; thanatophoric dysplasia typeII
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/32961
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