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 tiss ues and cell types, and the temporal expression of these receptors and thei r ligands play important roles in the control of development, There are fou r FGFR family members, FGFR-1-4, and understanding the ability of these rec eptors to transduce signals is central to understanding how they function i n controlling differentiation and development. We have utilized signal tran sduction 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 th e ability of FGFR-1 to induce robust and sustained activation of the Ras-de pendent mitogen-activated protein kinase pathways, In contrast, FGFR-3 coul d not induce strong sustained Ras-dependent signals. In this study, we anal yzed the ability of FGFR-3 to induce the expression of sodium channels, per ipherin, and Thy-1 in PC12 cells because all three of these proteins are kn own to be induced via Ras-independent pathways. We determined that FGFR-3 w as capable of inducing several Ras-independent gene expression pathways imp ortant to the neuronal phenotype to a level equivalent of that induced by F GFR-1. Thus, FGFR-3 elicits phenotypic changes primarily though activation of Ras-independent pathways in the absence of robust Ras-dependent signals.