Abstract
Proliferin (PLF) is a secreted glycoprotein in the prolactin-growth hormone family in mice. PLF expression was detected in C3H 10T1/2 fibroblasts, but not in two 10T1/2-derived myogenic cell lines, and was restored in two nondifferentiating variants of one of these myogenic cell lines. Transient expression of one form of PLF (PLF1) inhibited expression from a muscle-specific gene promoter; a second form of PLF, which differed at three amino acid residues, displayed no activity in this transient assay. Introduction of a PLF1 expression construct into both muscle- and 10T1/2-derived myoblasts resulted in cell lines that were no longer myogenic or that differentiated only partially. Analysis of these cell lines revealed that differentiation could be obstructed at several steps and by one or more factors in addition to PLF. Although expected to function in vivo as an extracellular hormone, PLF did not appear to be acting through a cell surface receptor to inhibit differentiation in these cultured myoblasts.
Full text
PDF











Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bader D., Masaki T., Fischman D. A. Immunochemical analysis of myosin heavy chain during avian myogenesis in vivo and in vitro. J Cell Biol. 1982 Dec;95(3):763–770. doi: 10.1083/jcb.95.3.763. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Blau H. M., Chiu C. P., Webster C. Cytoplasmic activation of human nuclear genes in stable heterocaryons. Cell. 1983 Apr;32(4):1171–1180. doi: 10.1016/0092-8674(83)90300-8. [DOI] [PubMed] [Google Scholar]
- 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]
- Chen C., Okayama H. High-efficiency transformation of mammalian cells by plasmid DNA. Mol Cell Biol. 1987 Aug;7(8):2745–2752. doi: 10.1128/mcb.7.8.2745. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
- Clegg C. H., Linkhart T. A., Olwin B. B., Hauschka S. D. Growth factor control of skeletal muscle differentiation: commitment to terminal differentiation occurs in G1 phase and is repressed by fibroblast growth factor. J Cell Biol. 1987 Aug;105(2):949–956. doi: 10.1083/jcb.105.2.949. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Davis R. L., Weintraub H., Lassar A. B. Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell. 1987 Dec 24;51(6):987–1000. doi: 10.1016/0092-8674(87)90585-x. [DOI] [PubMed] [Google Scholar]
- Denhardt D. T., Hamilton R. T., Parfett C. L., Edwards D. R., St Pierre R., Waterhouse P., Nilsen-Hamilton M. Close relationship of the major excreted protein of transformed murine fibroblasts to thiol-dependent cathepsins. Cancer Res. 1986 Sep;46(9):4590–4593. [PubMed] [Google Scholar]
- Gal S., Gottesman M. M. The major excreted protein of transformed fibroblasts is an activable acid-protease. J Biol Chem. 1986 Feb 5;261(4):1760–1765. [PubMed] [Google Scholar]
- Glisin V., Crkvenjakov R., Byus C. Ribonucleic acid isolated by cesium chloride centrifugation. Biochemistry. 1974 Jun 4;13(12):2633–2637. doi: 10.1021/bi00709a025. [DOI] [PubMed] [Google Scholar]
- Gorman C. M., Merlino G. T., Willingham M. C., Pastan I., Howard B. H. The Rous sarcoma virus long terminal repeat is a strong promoter when introduced into a variety of eukaryotic cells by DNA-mediated transfection. Proc Natl Acad Sci U S A. 1982 Nov;79(22):6777–6781. doi: 10.1073/pnas.79.22.6777. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Gorman C., Padmanabhan R., Howard B. H. High efficiency DNA-mediated transformation of primate cells. Science. 1983 Aug 5;221(4610):551–553. doi: 10.1126/science.6306768. [DOI] [PubMed] [Google Scholar]
- Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
- Jaynes J. B., Chamberlain J. S., Buskin J. N., Johnson J. E., Hauschka S. D. Transcriptional regulation of the muscle creatine kinase gene and regulated expression in transfected mouse myoblasts. Mol Cell Biol. 1986 Aug;6(8):2855–2864. doi: 10.1128/mcb.6.8.2855. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Konieczny S. F., Emerson C. P., Jr 5-Azacytidine induction of stable mesodermal stem cell lineages from 10T1/2 cells: evidence for regulatory genes controlling determination. Cell. 1984 Oct;38(3):791–800. doi: 10.1016/0092-8674(84)90274-5. [DOI] [PubMed] [Google Scholar]
- Konieczny S. F., Emerson C. P., Jr Differentiation, not determination, regulates muscle gene activation: transfection of troponin I genes into multipotential and muscle lineages of 10T1/2 cells. Mol Cell Biol. 1985 Sep;5(9):2423–2432. doi: 10.1128/mcb.5.9.2423. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
- Lassar A. B., Paterson B. M., Weintraub H. Transfection of a DNA locus that mediates the conversion of 10T1/2 fibroblasts to myoblasts. Cell. 1986 Dec 5;47(5):649–656. doi: 10.1016/0092-8674(86)90507-6. [DOI] [PubMed] [Google Scholar]
- Lathrop B., Olson E., Glaser L. Control by fibroblast growth factor of differentiation in the BC3H1 muscle cell line. J Cell Biol. 1985 May;100(5):1540–1547. doi: 10.1083/jcb.100.5.1540. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lee S. J., Nathans D. Proliferin secreted by cultured cells binds to mannose 6-phosphate receptors. J Biol Chem. 1988 Mar 5;263(7):3521–3527. [PubMed] [Google Scholar]
- Lee S. J., Nathans D. Secretion of proliferin. Endocrinology. 1987 Jan;120(1):208–213. doi: 10.1210/endo-120-1-208. [DOI] [PubMed] [Google Scholar]
- Lee S. J., Talamantes F., Wilder E., Linzer D. I., Nathans D. Trophoblastic giant cells of the mouse placenta as the site of proliferin synthesis. Endocrinology. 1988 May;122(5):1761–1768. doi: 10.1210/endo-122-5-1761. [DOI] [PubMed] [Google Scholar]
- Lehrach H., Diamond D., Wozney J. M., Boedtker H. RNA molecular weight determinations by gel electrophoresis under denaturing conditions, a critical reexamination. Biochemistry. 1977 Oct 18;16(21):4743–4751. doi: 10.1021/bi00640a033. [DOI] [PubMed] [Google Scholar]
- Linzer D. I., Lee S. J., Ogren L., Talamantes F., Nathans D. Identification of proliferin mRNA and protein in mouse placenta. Proc Natl Acad Sci U S A. 1985 Jul;82(13):4356–4359. doi: 10.1073/pnas.82.13.4356. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Linzer D. I., Levine A. J. Characterization of a 54K dalton cellular SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells. Cell. 1979 May;17(1):43–52. doi: 10.1016/0092-8674(79)90293-9. [DOI] [PubMed] [Google Scholar]
- Linzer D. I., Mordacq J. C. Transcriptional regulation of proliferin gene expression in response to serum in transfected mouse cells. EMBO J. 1987 Aug;6(8):2281–2288. doi: 10.1002/j.1460-2075.1987.tb02502.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Linzer D. I., Nathans D. Growth-related changes in specific mRNAs of cultured mouse cells. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4271–4275. doi: 10.1073/pnas.80.14.4271. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Linzer D. I., Nathans D. Nucleotide sequence of a growth-related mRNA encoding a member of the prolactin-growth hormone family. Proc Natl Acad Sci U S A. 1984 Jul;81(14):4255–4259. doi: 10.1073/pnas.81.14.4255. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Linzer D. I., Wilder E. L. Control of proliferin gene expression in serum-stimulated mouse cells. Mol Cell Biol. 1987 Jun;7(6):2080–2086. doi: 10.1128/mcb.7.6.2080. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lopata M. A., Cleveland D. W., Sollner-Webb B. High level transient expression of a chloramphenicol acetyl transferase gene by DEAE-dextran mediated DNA transfection coupled with a dimethyl sulfoxide or glycerol shock treatment. Nucleic Acids Res. 1984 Jul 25;12(14):5707–5717. doi: 10.1093/nar/12.14.5707. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Massagué J., Cheifetz S., Endo T., Nadal-Ginard B. Type beta transforming growth factor is an inhibitor of myogenic differentiation. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8206–8210. doi: 10.1073/pnas.83.21.8206. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Morgan D. O., Edman J. C., Standring D. N., Fried V. A., Smith M. C., Roth R. A., Rutter W. J. Insulin-like growth factor II receptor as a multifunctional binding protein. Nature. 1987 Sep 24;329(6137):301–307. doi: 10.1038/329301a0. [DOI] [PubMed] [Google Scholar]
- Nilsen-Hamilton M., Shapiro J. M., Massoglia S. L., Hamilton R. T. Selective stimulation by mitogens of incorporation of 35S-methionine into a family of proteins released into the medium by 3T3 cells. Cell. 1980 May;20(1):19–28. doi: 10.1016/0092-8674(80)90230-5. [DOI] [PubMed] [Google Scholar]
- Olson E. N., Spizz G., Tainsky M. A. The oncogenic forms of N-ras or H-ras prevent skeletal myoblast differentiation. Mol Cell Biol. 1987 Jun;7(6):2104–2111. doi: 10.1128/mcb.7.6.2104. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Parfett C. L., Hamilton R. T., Howell B. W., Edwards D. R., Nilsen-Hamilton M., Denhardt D. T. Characterization of a cDNA clone encoding murine mitogen-regulated protein: regulation of mRNA levels in mortal and immortal cell lines. Mol Cell Biol. 1985 Nov;5(11):3289–3292. doi: 10.1128/mcb.5.11.3289. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pinney D. F., Pearson-White S. H., Konieczny S. F., Latham K. E., Emerson C. P., Jr Myogenic lineage determination and differentiation: evidence for a regulatory gene pathway. Cell. 1988 Jun 3;53(5):781–793. doi: 10.1016/0092-8674(88)90095-5. [DOI] [PubMed] [Google Scholar]
- 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]
- Reznikoff C. A., Brankow D. W., Heidelberger C. Establishment and characterization of a cloned line of C3H mouse embryo cells sensitive to postconfluence inhibition of division. Cancer Res. 1973 Dec;33(12):3231–3238. [PubMed] [Google Scholar]
- Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
- Sahagian G. G., Gottesman M. M. The predominant secreted protein of transformed murine fibroblasts carries the lysosomal mannose 6-phosphate recognition marker. J Biol Chem. 1982 Sep 25;257(18):11145–11150. [PubMed] [Google Scholar]
- Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Southern P. J., Berg P. Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV40 early region promoter. J Mol Appl Genet. 1982;1(4):327–341. [PubMed] [Google Scholar]
- Sugden B., Marsh K., Yates J. A vector that replicates as a plasmid and can be efficiently selected in B-lymphoblasts transformed by Epstein-Barr virus. Mol Cell Biol. 1985 Feb;5(2):410–413. doi: 10.1128/mcb.5.2.410. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Taylor S. M., Jones P. A. Multiple new phenotypes induced in 10T1/2 and 3T3 cells treated with 5-azacytidine. Cell. 1979 Aug;17(4):771–779. doi: 10.1016/0092-8674(79)90317-9. [DOI] [PubMed] [Google Scholar]
- Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Webster K. A., Muscat G. E., Kedes L. Adenovirus E1A products suppress myogenic differentiation and inhibit transcription from muscle-specific promoters. Nature. 1988 Apr 7;332(6164):553–557. doi: 10.1038/332553a0. [DOI] [PubMed] [Google Scholar]
- Wigler M., Pellicer A., Silverstein S., Axel R., Urlaub G., Chasin L. DNA-mediated transfer of the adenine phosphoribosyltransferase locus into mammalian cells. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1373–1376. doi: 10.1073/pnas.76.3.1373. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wilder E. L., Linzer D. I. Expression of multiple proliferin genes in mouse cells. Mol Cell Biol. 1986 Sep;6(9):3283–3286. doi: 10.1128/mcb.6.9.3283. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wright W. E. Control of differentiation in heterokaryons and hybrids involving differentiation-defective myoblast variants. J Cell Biol. 1984 Feb;98(2):436–443. doi: 10.1083/jcb.98.2.436. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- von Figura K., Hasilik A. Lysosomal enzymes and their receptors. Annu Rev Biochem. 1986;55:167–193. doi: 10.1146/annurev.bi.55.070186.001123. [DOI] [PubMed] [Google Scholar]