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 differential display approach to identify fibroblast growth factor-1-inducible genes in murine NIH 3T3 cells. Here, we report that the fibroblast growth factor-inducible-14 (Fn14) gene is a growth factor-regulated, immediate-early response gene expressed in a developmental stage- and adult tissue-specific manner in vivo. This gene, located on mouse chromosome 17, is predicted to encode an 129-amino acid type Ia membrane protein with no significant sequence similarity to any known protein. We have used two experimental approaches, direct fluorescence microscopy and immunoprecipitation analysis of biotinylated cell surface proteins, to demonstrate that Fn14 is located on the plasma membrane. To examine the biological consequences of constitutive Fn14 expression, we isolated NIH 3T3 cell lines expressing variable levels of epitope-tagged Fn14 and analyzed their phenotypic properties in vitro. These experiments revealed that Fn14 expression decreased cellular adhesion to the extracellular matrix proteins fibronectin and vitronectin and also reduced serum-stimulated cell growth and migration. These results indicate that Fn14 is a novel plasma membrane-spanning molecule that may play a role in cell-matrix interactions.
Meighan-Mantha
R L
RL
Department of Vascular Biology, Holland Laboratory, American Red Cross, Rockville, Maryland 20855, USA.
Hsu
D K
DK
Guo
Y
Y
Brown
S A
SA
Feng
S L
SL
Peifley
K A
KA
Alberts
G F
GF
Copeland
N G
NG
Gilbert
D J
DJ
Jenkins
N A
NA
Richards
C M
CM
Winkles
J A
JA
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002448:Cell Adhesion / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004815:Epidermal Growth Factor / Q000235:genetics; D005109:Extracellular Matrix / Q000378:metabolism; D016220:Fibroblast Growth Factor 1; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006388:Hemagglutinins / Q000235:genetics; D017403:In Situ Hybridization; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D051379:Mice; D008856:Microscopy, Fluorescence; D008934:Mitogens / Q000494:pharmacology; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins / Q000235:genetics; D000074050:TWEAK Receptor; D014162:Transfection
D006388:Hemagglutinins; D008565:Membrane Proteins; D008934:Mitogens; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D000074050:TWEAK Receptor; C000613299:Tnfrsf12a protein, mouse; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D004815:Epidermal Growth Factor