Proceedings of the National Academy of Sciences · 1991 · 502 citations · 26 references
Life SciencesCell BiologyMolecular BiologyCell ProliferationCell SignalingSignal TransductionCell Signaling NetworksGrowth Factor SignalingMitogenic SignalingParacrine SignalingProtein SynthesisReceptor Tyrosine Kinase SignalingCell Proliferation SignalingHeparin-binding ProteinsHepatocyte Growth Factor SignalingMitogen SignalingMitogen-activated Protein Kinase SignalingMitogenic Signaling PathwaysProtein Tyrosine PhosphorylationTyrosine Phosphorylation Signaling
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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Molecular cloning and expression of human hepatocyte growth factor
Toshikazu Nakamura, Tsutomu Nishizawa, Mitchio Hagiya et al. · Nature · 1989 · 2.2K citations