The mitogen-inducible Fn14 gene encodes a type I transmembrane protein that modulates fibroblast adhesion and migration

The binding of polypeptide growth factors to their appropriate cell surface transmembrane receptors triggers numerous biochemical responses, including the transcriptional. activation of specific genes. We have used a differen tial display approach to identify fibroblast growth factor-1-inducible gene s in murine NIH 3T3 cells. Here, we report that the fibroblast growth facto rinducible-14 (Fn14) gene is a growth factor-regulated, immediate-early res ponse gene expressed in a developmental stage- and adult tissue-specific ma nner in vivo. This gene, located on mouse chromosome 17, is predicted to en code an 129-amino acid type Ia membrane protein with no significant sequenc e similarity to any known protein. me have used two experimental approaches , direct fluorescence microscopy and immunoprecipitation analysis of biotin ylated cell surface proteins, to demonstrate that Fn14 is located on the pl asma membrane. To examine the biological consequences of constitutive Fn14 expression, we isolated NIH 3T3 cell lines expressing variable levels of ep itope-tagged Fn14 and analyzed their phenotypic properties in vitro. These experiments revealed that Fn14 expression decreased cellular adhesion to th e extracellular matrix proteins fibronectin and vitronectin and also reduce d serum-stimulated cell growth and migration. These results indicate that F n14 is a novel plasma membrane-spanning molecule that may play a role in ce ll-matrix interactions.