The fibroblast growth factor receptor-1 is necessary for the induction of neurite outgrowth in PC12 cells by aFGF.
The PC12 subclone, fnr-PC12 cells, is defective in neurite outgrowth in response to acidic fibroblast growth factor (aFGF); however, its response to nerve growth factor (NGF) is normal. Examination of the expression of FGF receptors (FGFRs) revealed that although PC12 cells express FGFR-1, -3, and -4, fnr-PC12 cells have a reduced level of expression of FGFR-1 but not FGFR-3 and -4. Transfection of FGFR-1 into fnr-PC12 cells efficiently restored aFGF-induced neurite outgrowth, whereas transfection of FGFR-3 was much less efficient. Transfection of a chimeric receptor consisting of the extracellular domain of FGFR-3 fused to the transmembrane and intracellular domain of FGFR-1, termed FR31b, efficiently restored aFGF-induced neurite outgrowth. This demonstrates that the difference between these two receptors in their ability to induce neurite outgrowth is attributable to differences in the signaling capacity of their cytoplasmic domains. Activation of the chimeric receptor by aFGF induced a stronger and more persistent increase in the tyrosine phosphorylation of cellular proteins than did activation of FGFR-3 alone. In particular, the activation of MAP kinase by FR31b was more persistent than when activated by FGFR-3. This difference in signaling potential of FGFR-1 and -3 in fnr-PC12 cells may account for the difference in the potential for induction of neurite outgrowth. These results demonstrate that FGF-induced neurite outgrowth in PC12 cells occurs mainly via FGFR-1 and not via the other FGFRs expressed in these cells.
Lin
H Y
HY
Biochemistry and Molecular Biology Graduate Program, State University of New York at Stony Brook 11794, USA.
Xu
J
J
Ornitz
D M
DM
Halegoua
S
S
Hayman
M J
MJ
D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D006801:Humans; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000494:pharmacology; D016501:Neurites / Q000502:physiology*; D016716:PC12 Cells / Q000187:drug effects* / Q000502:physiology; D051381:Rats
D009414:Nerve Growth Factors; D016220:Fibroblast Growth Factor 1