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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 Mar 1;89(5):1715–1719. doi: 10.1073/pnas.89.5.1715

Isolation and sequence of the granulin precursor cDNA from human bone marrow reveals tandem cysteine-rich granulin domains.

V Bhandari 1, R G Palfree 1, A Bateman 1
PMCID: PMC48523  PMID: 1542665

Abstract

Granulins are candidate growth factors recently discovered in human and rat inflammatory leukocytes and bone marrow. Two granulin homologs, epithelin 1 and 2, occur in the rat kidney. Epithelin 1, which is probably identical to rat leukocyte granulin, exhibits proliferative and antiproliferative effects on epithelial cells in vitro. Here we show by cDNA analysis that the prepropeptide for the human granulins is a 593-residue glycoprotein, containing seven tandem repeats of the 12-cysteine granulin domain. By Northern blot analysis, gene expression was seen in myelogenous leukemic cell lines of promonocytic, promyelocytic, and proerythroid lineage, in fibroblasts and was seen very strongly in epithelial cell lines. Some epithelial cell lines respond to the mature peptide and express the gene. Among tissues examined, the kidney had the highest levels of granulin mRNA.

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Selected References

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  1. Assoian R. K., Fleurdelys B. E., Stevenson H. C., Miller P. J., Madtes D. K., Raines E. W., Ross R., Sporn M. B. Expression and secretion of type beta transforming growth factor by activated human macrophages. Proc Natl Acad Sci U S A. 1987 Sep;84(17):6020–6024. doi: 10.1073/pnas.84.17.6020. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Assoian R. K., Komoriya A., Meyers C. A., Miller D. M., Sporn M. B. Transforming growth factor-beta in human platelets. Identification of a major storage site, purification, and characterization. J Biol Chem. 1983 Jun 10;258(11):7155–7160. [PubMed] [Google Scholar]
  3. Baird A., Mormède P., Böhlen P. Immunoreactive fibroblast growth factor in cells of peritoneal exudate suggests its identity with macrophage-derived growth factor. Biochem Biophys Res Commun. 1985 Jan 16;126(1):358–364. doi: 10.1016/0006-291x(85)90614-x. [DOI] [PubMed] [Google Scholar]
  4. Bateman A., Belcourt D., Bennett H., Lazure C., Solomon S. Granulins, a novel class of peptide from leukocytes. Biochem Biophys Res Commun. 1990 Dec 31;173(3):1161–1168. doi: 10.1016/s0006-291x(05)80908-8. [DOI] [PubMed] [Google Scholar]
  5. Bateman A., Singh A., Congote L. F., Solomon S. The effect of HP-1 and related neutrophil granule peptides on DNA synthesis in HL60 cells. Regul Pept. 1991 Aug 13;35(2):135–143. doi: 10.1016/0167-0115(91)90476-w. [DOI] [PubMed] [Google Scholar]
  6. Bauer E. A., Cooper T. W., Huang J. S., Altman J., Deuel T. F. Stimulation of in vitro human skin collagenase expression by platelet-derived growth factor. Proc Natl Acad Sci U S A. 1985 Jun;82(12):4132–4136. doi: 10.1073/pnas.82.12.4132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bell G. I., Fong N. M., Stempien M. M., Wormsted M. A., Caput D., Ku L. L., Urdea M. S., Rall L. B., Sanchez-Pescador R. Human epidermal growth factor precursor: cDNA sequence, expression in vitro and gene organization. Nucleic Acids Res. 1986 Nov 11;14(21):8427–8446. doi: 10.1093/nar/14.21.8427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bevilacqua M. P., Stengelin S., Gimbrone M. A., Jr, Seed B. Endothelial leukocyte adhesion molecule 1: an inducible receptor for neutrophils related to complement regulatory proteins and lectins. Science. 1989 Mar 3;243(4895):1160–1165. doi: 10.1126/science.2466335. [DOI] [PubMed] [Google Scholar]
  9. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  10. Collins T., Williams A., Johnston G. I., Kim J., Eddy R., Shows T., Gimbrone M. A., Jr, Bevilacqua M. P. Structure and chromosomal location of the gene for endothelial-leukocyte adhesion molecule 1. J Biol Chem. 1991 Feb 5;266(4):2466–2473. [PubMed] [Google Scholar]
  11. Derynck R., Jarrett J. A., Chen E. Y., Eaton D. H., Bell J. R., Assoian R. K., Roberts A. B., Sporn M. B., Goeddel D. V. Human transforming growth factor-beta complementary DNA sequence and expression in normal and transformed cells. Nature. 1985 Aug 22;316(6030):701–705. doi: 10.1038/316701a0. [DOI] [PubMed] [Google Scholar]
  12. Freedman R. Protein chemistry. Folding into the right shape. Nature. 1987 Sep 17;329(6136):196–197. doi: 10.1038/329196a0. [DOI] [PubMed] [Google Scholar]
  13. Gray A., Dull T. J., Ullrich A. Nucleotide sequence of epidermal growth factor cDNA predicts a 128,000-molecular weight protein precursor. Nature. 1983 Jun 23;303(5919):722–725. doi: 10.1038/303722a0. [DOI] [PubMed] [Google Scholar]
  14. Grotendorst G. R., Smale G., Pencev D. Production of transforming growth factor beta by human peripheral blood monocytes and neutrophils. J Cell Physiol. 1989 Aug;140(2):396–402. doi: 10.1002/jcp.1041400226. [DOI] [PubMed] [Google Scholar]
  15. Gyllensten U. B., Erlich H. A. Generation of single-stranded DNA by the polymerase chain reaction and its application to direct sequencing of the HLA-DQA locus. Proc Natl Acad Sci U S A. 1988 Oct;85(20):7652–7656. doi: 10.1073/pnas.85.20.7652. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Higashiyama S., Abraham J. A., Miller J., Fiddes J. C., Klagsbrun M. A heparin-binding growth factor secreted by macrophage-like cells that is related to EGF. Science. 1991 Feb 22;251(4996):936–939. doi: 10.1126/science.1840698. [DOI] [PubMed] [Google Scholar]
  17. Ignotz R. A., Massagué J. Transforming growth factor-beta stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix. J Biol Chem. 1986 Mar 25;261(9):4337–4345. [PubMed] [Google Scholar]
  18. Kozak M. Compilation and analysis of sequences upstream from the translational start site in eukaryotic mRNAs. Nucleic Acids Res. 1984 Jan 25;12(2):857–872. doi: 10.1093/nar/12.2.857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kyte J., Doolittle R. F. A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982 May 5;157(1):105–132. doi: 10.1016/0022-2836(82)90515-0. [DOI] [PubMed] [Google Scholar]
  20. Lazure C., Seidah N. G., Pélaprat D., Chrétien M. Proteases and posttranslational processing of prohormones: a review. Can J Biochem Cell Biol. 1983 Jul;61(7):501–515. doi: 10.1139/o83-066. [DOI] [PubMed] [Google Scholar]
  21. Lee D. C., Rose T. M., Webb N. R., Todaro G. J. Cloning and sequence analysis of a cDNA for rat transforming growth factor-alpha. Nature. 1985 Feb 7;313(6002):489–491. doi: 10.1038/313489a0. [DOI] [PubMed] [Google Scholar]
  22. Lehrer R. I., Ganz T., Selsted M. E., Babior B. M., Curnutte J. T. Neutrophils and host defense. Ann Intern Med. 1988 Jul 15;109(2):127–142. doi: 10.7326/0003-4819-109-2-127. [DOI] [PubMed] [Google Scholar]
  23. MacLeod R. J., Hamilton J. R., Bateman A., Belcourt D., Hu J., Bennett H. P., Solomon S. Corticostatic peptides cause nifedipine-sensitive volume reduction in jejunal villus enterocytes. Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):552–556. doi: 10.1073/pnas.88.2.552. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. March C. J., Mosley B., Larsen A., Cerretti D. P., Braedt G., Price V., Gillis S., Henney C. S., Kronheim S. R., Grabstein K. Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs. Nature. 1985 Jun 20;315(6021):641–647. doi: 10.1038/315641a0. [DOI] [PubMed] [Google Scholar]
  25. Pennica D., Nedwin G. E., Hayflick J. S., Seeburg P. H., Derynck R., Palladino M. A., Kohr W. J., Aggarwal B. B., Goeddel D. V. Human tumour necrosis factor: precursor structure, expression and homology to lymphotoxin. Nature. 1984 Dec 20;312(5996):724–729. doi: 10.1038/312724a0. [DOI] [PubMed] [Google Scholar]
  26. Postlethwaite A. E., Keski-Oja J., Moses H. L., Kang A. H. Stimulation of the chemotactic migration of human fibroblasts by transforming growth factor beta. J Exp Med. 1987 Jan 1;165(1):251–256. doi: 10.1084/jem.165.1.251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Rall L. B., Scott J., Bell G. I., Crawford R. J., Penschow J. D., Niall H. D., Coghlan J. P. Mouse prepro-epidermal growth factor synthesis by the kidney and other tissues. Nature. 1985 Jan 17;313(5999):228–231. doi: 10.1038/313228a0. [DOI] [PubMed] [Google Scholar]
  28. Reibman J., Meixler S., Lee T. C., Gold L. I., Cronstein B. N., Haines K. A., Kolasinski S. L., Weissmann G. Transforming growth factor beta 1, a potent chemoattractant for human neutrophils, bypasses classic signal-transduction pathways. Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6805–6809. doi: 10.1073/pnas.88.15.6805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Ross R., Raines E. W., Bowen-Pope D. F. The biology of platelet-derived growth factor. Cell. 1986 Jul 18;46(2):155–169. doi: 10.1016/0092-8674(86)90733-6. [DOI] [PubMed] [Google Scholar]
  30. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  31. Scott J., Urdea M., Quiroga M., Sanchez-Pescador R., Fong N., Selby M., Rutter W. J., Bell G. I. Structure of a mouse submaxillary messenger RNA encoding epidermal growth factor and seven related proteins. Science. 1983 Jul 15;221(4607):236–240. doi: 10.1126/science.6602382. [DOI] [PubMed] [Google Scholar]
  32. Shimasaki S., Koga M., Esch F., Cooksey K., Mercado M., Koba A., Ueno N., Ying S. Y., Ling N., Guillemin R. Primary structure of the human follistatin precursor and its genomic organization. Proc Natl Acad Sci U S A. 1988 Jun;85(12):4218–4222. doi: 10.1073/pnas.85.12.4218. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Shoyab M., McDonald V. L., Byles C., Todaro G. J., Plowman G. D. Epithelins 1 and 2: isolation and characterization of two cysteine-rich growth-modulating proteins. Proc Natl Acad Sci U S A. 1990 Oct;87(20):7912–7916. doi: 10.1073/pnas.87.20.7912. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Sporn M. B., Roberts A. B. Peptide growth factors and inflammation, tissue repair, and cancer. J Clin Invest. 1986 Aug;78(2):329–332. doi: 10.1172/JCI112580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Territo M. C., Ganz T., Selsted M. E., Lehrer R. Monocyte-chemotactic activity of defensins from human neutrophils. J Clin Invest. 1989 Dec;84(6):2017–2020. doi: 10.1172/JCI114394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Tominaga T., Fukata J., Naito Y., Nakai Y., Funakoshi S., Fujii N., Imura H. Effects of corticostatin-I on rat adrenal cells in vitro. J Endocrinol. 1990 May;125(2):287–292. doi: 10.1677/joe.0.1250287. [DOI] [PubMed] [Google Scholar]
  37. Wahl S. M., Hunt D. A., Wakefield L. M., McCartney-Francis N., Wahl L. M., Roberts A. B., Sporn M. B. Transforming growth factor type beta induces monocyte chemotaxis and growth factor production. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5788–5792. doi: 10.1073/pnas.84.16.5788. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Zhu Q. Z., Hu J., Mulay S., Esch F., Shimasaki S., Solomon S. Isolation and structure of corticostatin peptides from rabbit fetal and adult lung. Proc Natl Acad Sci U S A. 1988 Jan;85(2):592–596. doi: 10.1073/pnas.85.2.592. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. von Heijne G. Signal sequences. The limits of variation. J Mol Biol. 1985 Jul 5;184(1):99–105. doi: 10.1016/0022-2836(85)90046-4. [DOI] [PubMed] [Google Scholar]

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