Gene expression and regulation of HGF-SF.
Molecular cloning and characterization of cDNAs and genomic DNA for human HGF-SF revealed the expression pattern of the gene. Alternative use of splicing sites and processing/polyadenylation sites generates multiple mRNAs for human HGF-SF in a variety of tissues and cell lines. This alternative mRNA production may be regulated in a tissue-specific manner. Full-length HGF-SF is encoded by the 6.3 kb or 3.1 kb mRNA. A variant form of HGF-SF is encoded by the 1.5 kb mRNA which is generated by alternative splicing accompanied by the utilization of an alternative processing/polyadenylation site in an extra exon. The variant form consists of an N-terminal sequence and the first two kringles and acts as an antagonist of HGF-SF mitogenic activity. HGF-SF with a deletion of 5 amino acids in the first kringle is produced from an alternatively spliced mRNA. The deletion induces the change in the heparin-binding property of the protein. Analysis of responses of the HGF-SF mRNA during liver regeneration revealed that the HGF-SF gene is activated. The level of mRNA markedly increases in the rat liver, spleen and lung after administration of hepatotoxins. Characteristic regulatory elements, an IL6 response element and an NF-IL6 binding element, are present proximal to the major transcription initiation site in the human HGF-SF gene. These elements may be involved in the activation of the gene after liver injury. The potential autocrine role of HGF-SF in the acquisition of altered phenotypes was determined by introduction of the gene into target cells for HGF-SF. Autocrine production of the factor induces changes in cell properties from parental types to those obtained by the addition of exogenous factor.
Kitamura
N
N
Institute for Liver Research, Kansai Medical University, Osaka, Japan.
Miyazawa
K
K
Uehara
Y
Y
Komada
M
M
Okajima
A
A
Okigaki
M
M
Kitamura
A
A
D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D015870:Gene Expression; D005786:Gene Expression Regulation; D014644:Genetic Variation; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D017384:Sequence Deletion; D016385:TATA Box; D014158:Transcription, Genetic
D012333:RNA, Messenger; D017228:Hepatocyte Growth Factor