Identification of a competitive HGF antagonist encoded by an alternative transcript.
We identified a naturally occurring hepatocyte growth factor (HGF) variant, whose predicted sequence extends only through the second kringle domain of this plasminogen-related molecule. This smaller molecule, derived from an alternative HGF transcript, lacked mitogenic activity but specifically inhibited HGF-induced mitogenesis. Cross-linking studies demonstrated that the truncated molecule competes with HGF for binding to the HGF receptor, which has been identified as the c-met protooncogene product. Thus, the same gene encodes both a growth factor and its direct antagonist.
Chan
A M
AM
Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, MD 20892.
Rubin
J S
JS
Bottaro
D P
DP
Hirschfield
D W
DW
Chedid
M
M
Aaronson
S A
SA
D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D002460:Cell Line; D003470:Culture Media; D004247:DNA / Q000235:genetics; D004261:DNA Replication / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006133:Growth Substances / Q000235:genetics* / Q000302:isolation & purification / Q000494:pharmacology; D017228:Hepatocyte Growth Factor; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010957:Plasmids; D011061:Poly A / Q000235:genetics / Q000302:isolation & purification; D016133:Polymerase Chain Reaction / Q000379:methods; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger; D013936:Thymidine / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
D003470:Culture Media; D006133:Growth Substances; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D011061:Poly A; D004815:Epidermal Growth Factor; D012313:RNA; D017228:Hepatocyte Growth Factor; D004247:DNA; D013936:Thymidine