Hepatocyte growth factor (HGF) receptor expression is inducible and is part of the delayed-early response to HGF.

The c-MET proto-oncogene encodes the tyrosine kinase receptor for hepatocyte growth factor (HGF), also known as scatter factor, a potent mitogen and motogen for epithelial cells. The level of the HGF receptor expressed by epithelial cells varies in different growth conditions, being lower in growth arrested confluent monolayers and higher in growing sparse cells. The amount of HGF receptor mRNA increases from 3- to 5-fold after stimulation of confluent monolayers by serum and up to 10-fold after stimulation of protein kinase C by 12-O-tetradecanoylphorbol-13-acetate (TPA). An increased level of the receptor mRNA was also observed after cell stimulation with nanomolar concentration of HGF itself. The effect was transient, dose, and time-dependent. Transcription of a reporter gene under control of the cloned 297 base pair c-MET promoter was also stimulated by serum, TPA, or HGF. The accumulation of specific mRNA is followed by appearance of the HGF receptor precursor protein, which is further processed to the receptor mature form. After HGF stimulation, HGF receptor expression follows c-FOS and c-JUN induction with a peak approximately 4 h. Pretreatment with the protein synthesis inhibitor puromycin strongly reduced the response to HGF, while cycloheximide alone increased the level of the receptor mRNA. These data show that c-MET behaves as a delayed early-response gene and suggest that the HGF response is autoamplified by inducing the specific receptor.

• Publication year

  1994

• Venue

  Journal of Biological Chemistry

• Publication date

  1994-04-29

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/s0021-9258(18)99953-9PMID 8175699
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• Puromycin strongly reduces the HGF response, whereas cycloheximide alone increases HGF receptor mRNA.

  Confidence 0.95

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• HGF receptor expression follows c-FOS and c-JUN induction and fits a delayed-early response program that can be autoamplified by HGF-induced receptor expression.

  Confidence 0.90

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• A cloned 297 bp c-MET promoter fragment drives reporter gene transcription that is stimulated by serum, TPA, or HGF.

  Confidence 0.94

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• Serum and TPA stimulation increase HGF receptor mRNA, with about 3- to 5-fold induction after serum and up to 10-fold induction after TPA in confluent monolayers.

  Confidence 0.98

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• HGF stimulation induces HGF receptor mRNA in epithelial cells in a transient, dose-dependent, and time-dependent manner.

  Confidence 0.97

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review

• 12-o-tetradecanoylphorbol-13-acetate (tpa)

  chemical, stimulus

  A phorbol ester used here as a protein kinase C activator to stimulate cellular signaling.

  Aliases: TPA, phorbol ester

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• c-fos and c-jun

  genes, transcription factors

  Immediate-early transcription factors used here as reference genes for the timing of the HGF response.

  Aliases: c-FOS, c-JUN

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• c-met promoter

  promoter, DNA element

  A cloned 297 base pair promoter fragment from c-MET used to test transcriptional regulation in a reporter construct.

  Aliases: MET promoter, 297 bp c-MET promoter

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• c-met proto-oncogene

  gene

  The gene encoding the receptor tyrosine kinase for hepatocyte growth factor in epithelial cells.

  Aliases: MET, c-MET

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• cycloheximide

  chemical, inhibitor

  A translation inhibitor used to test how blocking protein synthesis affects HGF receptor mRNA levels.

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• delayed-early response gene

  gene class

  A gene class induced after immediate-early signaling, bridging early stimulation and later transcriptional output.

  Aliases: late immediate-early response gene

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• hepatocyte growth factor

  protein, growth factor

  A signaling ligand, also called scatter factor, that binds the MET receptor on epithelial cells.

  Aliases: HGF, scatter factor

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• hgf receptor mrna

  mRNA, transcript

  The messenger RNA transcript encoding the hepatocyte growth factor receptor measured in epithelial cells.

  Aliases: MET mRNA, HGF receptor transcript

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• puromycin

  chemical, inhibitor

  A protein synthesis inhibitor used to probe whether the HGF response depends on new translation.

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• serum

  stimulus, biological sample

  Growth medium supplement used as a mitogenic stimulus for confluent epithelial monolayers in the experiments.

  Aliases: serum stimulation

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review

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  1994cited by this paper
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