Skip to main content

Some NLM-NCBI services and products are experiencing heavy traffic, which may affect performance and availability. We apologize for the inconvenience and appreciate your patience. For assistance, please contact our Help Desk at info@ncbi.nlm.nih.gov.

Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1989 May;9(5):2251–2253. doi: 10.1128/mcb.9.5.2251

The alternatively spliced exon of the platelet-derived growth factor A chain encodes a nuclear targeting signal.

D W Maher 1, B A Lee 1, D J Donoghue 1
PMCID: PMC363024  PMID: 2747650

Abstract

We have previously shown that the SIS/platelet-derived growth factor B chain contains a nuclear targeting signal near its C terminus. Here we show that the platelet-derived growth factor A chain also contains a nuclear targeting signal encoded by an exon which is subject to alternative splicing. This sequence is capable of targeting a nonsecreted form of the A chain to the nucleus and can also target the cytoplasmic proteins dihydrofolate reductase, chloramphenicol acetyltransferase, and pyruvate kinase to the nucleus.

Full text

PDF
2251

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beckmann M. P., Betsholtz C., Heldin C. H., Westermark B., Di Marco E., Di Fiore P. P., Robbins K. C., Aaronson S. A. Comparison of biological properties and transforming potential of human PDGF-A and PDGF-B chains. Science. 1988 Sep 9;241(4871):1346–1349. doi: 10.1126/science.2842868. [DOI] [PubMed] [Google Scholar]
  2. Betsholtz C., Johnsson A., Heldin C. H., Westermark B., Lind P., Urdea M. S., Eddy R., Shows T. B., Philpott K., Mellor A. L. cDNA sequence and chromosomal localization of human platelet-derived growth factor A-chain and its expression in tumour cell lines. Nature. 1986 Apr 24;320(6064):695–699. doi: 10.1038/320695a0. [DOI] [PubMed] [Google Scholar]
  3. Bonner W. M. Protein migration into nuclei. I. Frog oocyte nuclei in vivo accumulate microinjected histones, allow entry to small proteins, and exclude large proteins. J Cell Biol. 1975 Feb;64(2):421–430. doi: 10.1083/jcb.64.2.421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bonthron D. T., Morton C. C., Orkin S. H., Collins T. Platelet-derived growth factor A chain: gene structure, chromosomal location, and basis for alternative mRNA splicing. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1492–1496. doi: 10.1073/pnas.85.5.1492. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bouche G., Gas N., Prats H., Baldin V., Tauber J. P., Teissié J., Amalric F. Basic fibroblast growth factor enters the nucleolus and stimulates the transcription of ribosomal genes in ABAE cells undergoing G0----G1 transition. Proc Natl Acad Sci U S A. 1987 Oct;84(19):6770–6774. doi: 10.1073/pnas.84.19.6770. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Collins T., Bonthron D. T., Orkin S. H. Alternative RNA splicing affects function of encoded platelet-derived growth factor A chain. Nature. 1987 Aug 13;328(6131):621–624. doi: 10.1038/328621a0. [DOI] [PubMed] [Google Scholar]
  7. Doolittle R. F., Hunkapiller M. W., Hood L. E., Devare S. G., Robbins K. C., Aaronson S. A., Antoniades H. N. Simian sarcoma virus onc gene, v-sis, is derived from the gene (or genes) encoding a platelet-derived growth factor. Science. 1983 Jul 15;221(4607):275–277. doi: 10.1126/science.6304883. [DOI] [PubMed] [Google Scholar]
  8. Feng D. F., Doolittle R. F. Progressive sequence alignment as a prerequisite to correct phylogenetic trees. J Mol Evol. 1987;25(4):351–360. doi: 10.1007/BF02603120. [DOI] [PubMed] [Google Scholar]
  9. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gould S. G., Keller G. A., Subramani S. Identification of a peroxisomal targeting signal at the carboxy terminus of firefly luciferase. J Cell Biol. 1987 Dec;105(6 Pt 2):2923–2931. doi: 10.1083/jcb.105.6.2923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. James R., Bradshaw R. A. Polypeptide growth factors. Annu Rev Biochem. 1984;53:259–292. doi: 10.1146/annurev.bi.53.070184.001355. [DOI] [PubMed] [Google Scholar]
  12. Kozak M. Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes. Cell. 1986 Jan 31;44(2):283–292. doi: 10.1016/0092-8674(86)90762-2. [DOI] [PubMed] [Google Scholar]
  13. Lee B. A., Maher D. W., Hannink M., Donoghue D. J. Identification of a signal for nuclear targeting in platelet-derived-growth-factor-related molecules. Mol Cell Biol. 1987 Oct;7(10):3527–3537. doi: 10.1128/mcb.7.10.3527. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Miller D. S. Stimulation of RNA and protein synthesis by intracellular insulin. Science. 1988 Apr 22;240(4851):506–509. doi: 10.1126/science.2451860. [DOI] [PubMed] [Google Scholar]
  15. Rakowicz-Szulczynska E. M., Rodeck U., Herlyn M., Koprowski H. Chromatin binding of epidermal growth factor, nerve growth factor, and platelet-derived growth factor in cells bearing the appropriate surface receptors. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3728–3732. doi: 10.1073/pnas.83.11.3728. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Rorsman F., Bywater M., Knott T. J., Scott J., Betsholtz C. Structural characterization of the human platelet-derived growth factor A-chain cDNA and gene: alternative exon usage predicts two different precursor proteins. Mol Cell Biol. 1988 Feb;8(2):571–577. doi: 10.1128/mcb.8.2.571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ross R. Platelet-derived growth factor. Annu Rev Med. 1987;38:71–79. doi: 10.1146/annurev.me.38.020187.000443. [DOI] [PubMed] [Google Scholar]
  18. Subramani S., Mulligan R., Berg P. Expression of the mouse dihydrofolate reductase complementary deoxyribonucleic acid in simian virus 40 vectors. Mol Cell Biol. 1981 Sep;1(9):854–864. doi: 10.1128/mcb.1.9.854. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Tong B. D., Auer D. E., Jaye M., Kaplow J. M., Ricca G., McConathy E., Drohan W., Deuel T. F. cDNA clones reveal differences between human glial and endothelial cell platelet-derived growth factor A-chains. Nature. 1987 Aug 13;328(6131):619–621. doi: 10.1038/328619a0. [DOI] [PubMed] [Google Scholar]
  20. Yeh H. J., Pierce G. F., Deuel T. F. Ultrastructural localization of a platelet-derived growth factor/v-sis-related protein(s) in cytoplasm and nucleus of simian sarcoma virus-transformed cells. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2317–2321. doi: 10.1073/pnas.84.8.2317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. de Wet J. R., Wood K. V., DeLuca M., Helinski D. R., Subramani S. Firefly luciferase gene: structure and expression in mammalian cells. Mol Cell Biol. 1987 Feb;7(2):725–737. doi: 10.1128/mcb.7.2.725. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES