Cell adaptation to activated FGFR3 includes Sprouty4 up regulation to inhibit the receptor-mediated ERKs activation from the endoplasmic reticulum.
The kinase activity of the thanatophoric dysplasia type II-fibroblast growth factor receptor 3 mutant (TDII-FGFR3) hampers its maturation. As a consequence, the immature receptor activates extracellular regulated kinases (ERKs) from the endoplasmic reticulum (ER), which leads to apoptosis. On the other hand, in stable TDII-FGFR3 cells receptor biosynthesis is restored and ERKs are activated from the cell surface. To identify potential mediators of cell adaptation to the activated receptor we investigated gene products that are differently regulated in TDII and wild-type FGFR3 cells. cDNA representational difference analysis reveals Sprouty4 up regulation in the TDII-FGFR3 cells. Interestingly, 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, which silences the premature receptor signaling and suppress apoptosis.
Lievens
Patricia M-J
PM
Department of Morphological and Biomedical Sciences, Division of Biochemistry, University of Verona Medical School, Verona, Italy.
Zanolli
Elena
E
Garofalo
Silvio
S
Liboi
Elio
E
D017209:Apoptosis / Q000235:genetics; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000378:metabolism*; D013796:Thanatophoric Dysplasia / Q000201:enzymology / Q000235:genetics; D015854:Up-Regulation
D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; C499038:SPRY4 protein, human; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3; D048049:Extracellular Signal-Regulated MAP Kinases