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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 Jan 15;88(2):415–419. doi: 10.1073/pnas.88.2.415

A broad-spectrum human lung fibroblast-derived mitogen is a variant of hepatocyte growth factor.

J S Rubin 1, A M Chan 1, D P Bottaro 1, W H Burgess 1, W G Taylor 1, A C Cech 1, D W Hirschfield 1, J Wong 1, T Miki 1, P W Finch 1, et al.
PMCID: PMC50821  PMID: 1824873

Abstract

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.

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