Human keratinocytes and tumor-derived cell lines express alternatively spliced forms of transforming growth factor-alpha mRNA, encoding precursors lacking carboxyl-terminal valine residues.
Oncogene
; 18(40): 5554-62, 1999 Sep 30.
Article
em En
| MEDLINE
| ID: mdl-10523832
ABSTRACT
The human transforming growth factor-alpha (TGF-alpha) gene is thought to contain five introns and six exons, encoding a transmembrane precursor (proTGF-alpha) from which the mature polypeptide is released by proteolytic cleavage. We identified a novel 32-nucleotide exon (exon alpha) within intron 5 and an alternative splice acceptor site in exon 6, splitting exon 6 into two segments 6A and 6B. Therefore, in addition to wild type (wt) proTGF-alpha mRNA, which skips exon alpha, two novel proTGF-alpha variants are produced Variant I (VaI), skipping exons alpha and 6A, and Variant II (VaII) which includes exon alpha and skips exon 6A. The only significant difference between variant and wt proTGF-alpha proteins is that the two wt carboxyl-terminal valines are replaced in the variants by five or four other amino acids, respectively. Both variant TGF-alpha mRNAs were readily detected in human keratinocytes and tumor-derived cell lines. Their protein products were cleaved as efficiently as wt TGF-alpha in response to the calcium ionophore A23187. However, both variants (but not wt) reduced serum requirements for proliferation in CHO cells. In addition, VaII-expressing CHO cells (not VaI or wt) formed foci in monolayer cultures. These results suggest that variant TGF-alpha precursors induce autonomous growth.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
RNA Mensageiro
/
Queratinócitos
/
Splicing de RNA
/
Fator de Crescimento Transformador alfa
/
Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Oncogene
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Ano de publicação:
1999
Tipo de documento:
Article
País de afiliação:
Estados Unidos