Polypeptide growth factors and phorbol ester induce progressive ankylosis (ank) gene expression in murine and human fibroblasts.
Polypeptide growth factors promote cellular proliferation by binding to specific plasma membrane-anchored receptors. This interaction triggers the phosphorylation of signal transducing molecules and the transcriptional activation of numerous genes. We have used a differential display approach to identify fibroblast growth factor (FGF)-1-inducible genes in murine NIH 3T3 fibroblasts. Here we report that one of these genes encodes ank, a type IIIa transmembrane protein reported to function in cells as an inorganic pyrophosphate transporter. FGF-1 induction of ank mRNA expression is first detectable at 2 h after growth factor addition and is dependent on de novo RNA and protein synthesis. Ank gene expression is also upregulated after treating quiescent fibroblasts with several other mitogenic agents (e.g., calf serum or platelet-derived growth factor-BB) or the tumor promoter phorbol 12-myristate 13-acetate. Furthermore, in comparison to parental NIH 3T3 cells, oncogene-transformed NIH 3T3 cells constitutively express elevated levels of ank mRNA. FGF-1 also increases ank gene expression in non-immortalized human embryonic lung fibroblasts. Finally, the murine and human ank genes are expressed in vivo in a tissue-specific manner, with highest levels of mRNA expression found in brain, heart, and skeletal muscle. These results indicate that ank is a growth factor-regulated delayed-early response gene in mammalian cells, and we propose that increased ank expression during cell cycle progression may be necessary to maintain proper intracellular pyrophosphate levels during conditions of high cellular metabolic activity.
Guo
Y
Y
Department of Vascular Biology, Holland Laboratory, American Red Cross, Rockville, Maryland 20855, USA.
Hsu
D K
DK
Feng
S L
SL
Richards
C M
CM
Winkles
J A
JA
D016475:3T3 Cells; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology; D002461:Cell Line, Transformed; D018076:DNA, Complementary / Q000032:analysis / Q000302:isolation & purification; D004622:Embryo, Mammalian / Q000378:metabolism; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D010703:Phorbol Esters / Q000494:pharmacology*; D028061:Phosphate Transport Proteins; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D014018:Tissue Distribution
C498770:ANKH protein, human; D002273:Carcinogens; D018076:DNA, Complementary; D008565:Membrane Proteins; D010703:Phorbol Esters; D028061:Phosphate Transport Proteins; D012333:RNA, Messenger; C410982:ank protein, mouse; D016220:Fibroblast Growth Factor 1