FGFR3 isoforms have distinct functions in the regulation of growth and cell morphology

We have previously cloned the alternatively spliced isoform of fibroblast growth factor receptor 3 (FGFR3DeltaAB) that lacks the acid box in the extracellular region. To understand the biological functions and signal transduction of these FGFR3 isoforms, we analyzed the effect of FGF1 in ATDC5 cells, chondroprogenitor cell lines overexpressing these isoforms. In response to FGF1, FGFR3 induced a marked cell-morphology change to a round shape, while FGFR3DeltaAB did not. Furthermore, FGFR3 induced complete growth arrest, whereas FGFR3DeltaAB induced only moderate growth inhibition. Both receptors induced the expression of the CDK inhibitor p21(CIP1). However, only FGFR3 induced STAT1 phosphorylation that mediates the transcriptional induction of p21(CIP1), although both FGFR3 isoforms could induce a strong activation of mitogen-activated protein (MAP) kinases. Taken together, the different biological responses mediated by FGFR3 and FGFR3DeltaAB appear to be due to a difference in their ability to utilize STAT1 pathway and signals involved in cell rounding.