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Science 3 February 1984:
Vol. 223. no. 4635, pp. 487 - 491
DOI: 10.1126/science.6318322
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Articles

Science, Vol 223, Issue 4635, 487-491
Copyright © 1984 by American Association for the Advancement of Science

articles

Human-proto-oncogene nucleotide sequences corresponding to the transforming region of simian sarcoma virus

SF Josephs, C Guo, L Ratner, and F Wong-Staal

The nucleotide sequences of the six regions within the normal human cellular locus (c-sis) that correspond to the entire transforming region of the simian sarcoma virus (SSV) genome (v-sis) were determined. The regions are bounded by acceptor and donor splice sites and, except for region 6, resemble exons. Region 6 lacks a 3' donor splice site and terminates -5 base pairs from the 3' v-sis-helper-viral junction. This is consistent with a model proposing that SSV was generated by recombination between proviral DNA of a simian sarcoma associated virus and proto-sis and that introns were spliced out subsequently from a fused viral-sis messenger RNA. This also suggests that the 3' recombination occurred within an exon of the woolly monkey (Lagothrix) genome. The open reading frames predicting the v-sis and c-sis gene products coincide with the stop codon of c-sis located 123 nucleotides into the fifth region of homology. The overall nucleotide homology was 91 percent with substitutions mainly in the third codon positions within the open reading frame and with greatest divergence within the untranslated 3' portion of the sequences. The predicted protein products for v-sis and c-sis are 93 percent homologous. The predicted c-sis gene product is identical in 31 of 31 amino acids to one of the published sequences of platelet-derived growth factor. Thus, c-sis encodes one chain of human platelet-derived growth factor.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Comparison of biological properties and transforming potential of human PDGF-A and PDGF-B chains.
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Science 241, 1346-1349
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Autocrine stimulation of intracellular PDGF receptors in v-sis-transformed cells.
M. Keating and L. Williams (1988)
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Oncogenic Potential of the Human Platelet-derived Growth Factor Transcriptional Unit.
C.D. Rao, H. Igarashi, M.W. Pech, K.C. Robbins, and S.A. Aaronson (1986)
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Evidence that the v-sis gene product transforms by interaction with the receptor for platelet-derived growth factor.
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The mosaic genome of warm-blooded vertebrates.
G Bernardi, B Olofsson, J Filipski, M Zerial, J Salinas, G Cuny, M Meunier-Rotival, and F Rodier (1985)
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Requirement for a signal sequence in biological expression of the v-sis oncogene.
M Hannink and D. Donoghue (1984)
Science 226, 1197-1199
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Detection of c-sis transcripts and synthesis of PDGF-like proteins by human osteosarcoma cells.
D. Graves, A. Owen, R. Barth, P Tempst, A Winoto, L Fors, L. Hood, and H. Antoniades (1984)
Science 226, 972-974
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Detection of high molecular weight forms of platelet-derived growth factor by sequence-specific antisera.
H. Niman, R. Houghten, and D. Bowen-Pope (1984)
Science 226, 701-703
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Transforming potential of human c-sis nucleotide sequences encoding platelet-derived growth factor.
S. Josephs, L Ratner, M. Clarke, E. Westin, M. Reitz, and F Wong-Staal (1984)
Science 225, 636-639
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