A broad-spectrum human lung fibroblast-derived mitogen is a variant of hepatocyte growth factor.
A heparin-binding mitogen was isolated from conditioned medium of human embryonic lung fibroblasts. It exhibited broad target-cell specificity whose pattern was distinct from that of any known growth factor. It rapidly stimulated tyrosine phosphorylation of a 145-kDa protein in responsive cells, suggesting that its signaling pathways involved activation of a tyrosine kinase. Purification identified a major polypeptide with an apparent molecular mass of 87 kDa under reducing conditions. Partial amino acid sequence analysis and cDNA cloning revealed that it was a variant of hepatocyte growth factor, a mitogen thought to be specific for hepatic cells and structurally related to plasminogen. Recombinant expression of the cDNA in COS-1 cells established that it encoded the purified growth factor. Its site of synthesis and spectrum of targets imply that this growth factor may play an important role as a paracrine mediator of the proliferation of melanocytes and endothelial cells, as well as cells of epithelial origin.
Rubin
J S
JS
Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, MD 20892.
Chan
A M
AM
Bottaro
D P
DP
Burgess
W H
WH
Taylor
W G
WG
Cech
A C
AC
Hirschfield
D W
DW
Wong
J
J
Miki
T
T
Finch
P W
PW
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D004261:DNA Replication / Q000187:drug effects*; D004789:Enzyme Activation; D005347:Fibroblasts / Q000378:metabolism; D014644:Genetic Variation; D006133:Growth Substances / Q000235:genetics*; D017228:Hepatocyte Growth Factor; D006801:Humans; D007700:Kinetics; D008168:Lung; D051379:Mice; D008815:Mice, Inbred Strains; D008934:Mitogens / Q000235:genetics* / Q000302:isolation & purification; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015183:Restriction Mapping; D014162:Transfection
D006133:Growth Substances; C066855:HGF protein, human; D008934:Mitogens; D015345:Oligonucleotide Probes; D011994:Recombinant Proteins; D017228:Hepatocyte Growth Factor; D004247:DNA; D011505:Protein-Tyrosine Kinases