Abstract
Hepatocyte growth factor/scatter factor (HGF/SF) is a multifunctional factor that stimulates epithelial cell mitogenesis, motility, invasion, and morphogenesis. Its receptor is encoded by the MET proto-oncogene, a transmembrane receptor tyrosine kinase. Several studies have suggested a role for MET as a dominant oncogene in tumor development and progression. Conversely, MET is located at a region on chromosome 7q31 frequently deleted in carcinomas, suggesting that recessive mutations in MET may exist in certain cancers. To facilitate a search for mutations in MET, we have obtained the intron-exon structure of the human MET gene. We present the genomic structure of the first member of the Met receptor family to be characterized. Interestingly, MET contains a large second exon of 1214 nucleotides. We show that this exon, containing the AUG for the Met receptor, is frequently skipped in normal human tissues and cell lines, and corresponds to a ubiquitously expressed 7 kb Met transcript. This transcript yields no detectable protein product in vivo. Thus, unlike other genes, in which alternative splicing often gives rise to proteins with distinct activities, exon-skipping of MET exon 2 is predicted to decrease the abundance of a Met mRNA encoding a functional Met receptor.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lin, J., Naujokas, M., Zhu, H. et al. Intron-exon structure of the MET gene and cloning of an alternatively-spliced Met isoform reveals frequent exon-skipping of a single large internal exon. Oncogene 16, 833–842 (1998). https://doi.org/10.1038/sj.onc.1201599
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1201599
Keywords
This article is cited by
-
Overcoming resistance to targeted therapy using MET inhibitors in solid cancers: evidence from preclinical and clinical studies
Medical Oncology (2021)
-
Multiplexed, targeted profiling of single-cell proteomes and transcriptomes in a single reaction
Genome Biology (2016)
-
MET and autism susceptibility: family and case–control studies
European Journal of Human Genetics (2009)
-
Mapping of the 7q31 subregion common to the small chromosome 7 derivatives from two sporadic papillary renal cell carcinomas: increased copy number and overexpression of the MET proto-oncogene
Oncogene (2000)