Fibroblast growth factor receptor 3 induces gene expression primarily through Ras-independent signal transduction pathways.
Fibroblast growth factor receptors (FGFR) are widely expressed in many tissues and cell types, and the temporal expression of these receptors and their ligands play important roles in the control of development. There are four FGFR family members, FGFR-1-4, and understanding the ability of these receptors to transduce signals is central to understanding how they function in controlling differentiation and development. We have utilized signal transduction by FGF-1 in PC12 cells to compare the ability of FGFR-1 and FGFR-3 to elicit the neuronal phenotype. In PC12 cells FGFR-1 is much more potent in the induction of neurite outgrowth than FGFR-3. This correlated with the ability of FGFR-1 to induce robust and sustained activation of the Ras-dependent mitogen-activated protein kinase pathways. In contrast, FGFR-3 could not induce strong sustained Ras-dependent signals. In this study, we analyzed the ability of FGFR-3 to induce the expression of sodium channels, peripherin, and Thy-1 in PC12 cells because all three of these proteins are known to be induced via Ras-independent pathways. We determined that FGFR-3 was capable of inducing several Ras-independent gene expression pathways important to the neuronal phenotype to a level equivalent of that induced by FGFR-1. Thus, FGFR-3 elicits phenotypic changes primarily though activation of Ras-independent pathways in the absence of robust Ras-dependent signals.
Choi
D Y
DY
Department of Molecular Genetics and Microbiology, Institute of Cell and Developmental Biology, State University of New York at Stony Brook, Stony Brook, NY 11794-5222, USA.
Toledo-Aral
J J
JJ
Lin
H Y
HY
Ischenko
I
I
Medina
L
L
Safo
P
P
Mandel
G
G
Levinson
S R
SR
Halegoua
S
S
Hayman
M J
MJ
D000818:Animals; D002470:Cell Survival; D016220:Fibroblast Growth Factor 1; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D007381:Intermediate Filament Proteins / Q000096:biosynthesis / Q000235:genetics; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis / Q000235:genetics; D008562:Membrane Glycoproteins; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D016716:PC12 Cells; D018408:Patch-Clamp Techniques; D064531:Peripherins; D011505:Protein-Tyrosine Kinases; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D015398:Signal Transduction; D015222:Sodium Channels / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D018800:Thy-1 Antigens / Q000096:biosynthesis / Q000235:genetics; D015533:Transcriptional Activation
D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D064531:Peripherins; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D015222:Sodium Channels; D018800:Thy-1 Antigens; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; C496350:Fgfr1 protein, rat; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051498:Receptor, Fibroblast Growth Factor, Type 3; D019278:Matrix Metalloproteinase 3; D016283:Proto-Oncogene Proteins p21(ras)