Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1990 Sep 1;172(3):911–919. doi: 10.1084/jem.172.3.911

Cloning and characterization of cDNAs for murine macrophage inflammatory protein 2 and its human homologues

PMCID: PMC2188540  PMID: 2201751

Abstract

A cDNA clone of murine macrophage inflammatory protein 2 (MIP-2) has been isolated from a library prepared from lipopolysaccharide (LPS)- stimulated RAW 264.7 cells and the nucleotide sequence determined. This cDNA was used to clone cDNAs for human homologues of MIP-2 from a library prepared from phorbol myristate acetate-treated and LPS- stimulated U937 cells. Two homologues were isolated and sequenced. Human MIP-2 alpha and MIP-2 beta are highly homologous to each other and to a previously isolated gene, human gro/melanoma growth- stimulating activity (MGSA). These three human genes, MIP-2 alpha, MIP- 2 beta, and gro/MGSA, constitute a sub-family within the cytokine family represented by platelet factor 4 and interleukin 8.

Full Text

The Full Text of this article is available as a PDF (999.5 KB).

Selected References

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

  1. Anisowicz A., Bardwell L., Sager R. Constitutive overexpression of a growth-regulated gene in transformed Chinese hamster and human cells. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7188–7192. doi: 10.1073/pnas.84.20.7188. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Anisowicz A., Zajchowski D., Stenman G., Sager R. Functional diversity of gro gene expression in human fibroblasts and mammary epithelial cells. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9645–9649. doi: 10.1073/pnas.85.24.9645. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bedard P. A., Alcorta D., Simmons D. L., Luk K. C., Erikson R. L. Constitutive expression of a gene encoding a polypeptide homologous to biologically active human platelet protein in Rous sarcoma virus-transformed fibroblasts. Proc Natl Acad Sci U S A. 1987 Oct;84(19):6715–6719. doi: 10.1073/pnas.84.19.6715. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Birnstiel M. L., Busslinger M., Strub K. Transcription termination and 3' processing: the end is in site! Cell. 1985 Jun;41(2):349–359. doi: 10.1016/s0092-8674(85)80007-6. [DOI] [PubMed] [Google Scholar]
  5. Broxmeyer H. E., Sherry B., Lu L., Cooper S., Carow C., Wolpe S. D., Cerami A. Myelopoietic enhancing effects of murine macrophage inflammatory proteins 1 and 2 on colony formation in vitro by murine and human bone marrow granulocyte/macrophage progenitor cells. J Exp Med. 1989 Nov 1;170(5):1583–1594. doi: 10.1084/jem.170.5.1583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Caput D., Beutler B., Hartog K., Thayer R., Brown-Shimer S., Cerami A. Identification of a common nucleotide sequence in the 3'-untranslated region of mRNA molecules specifying inflammatory mediators. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1670–1674. doi: 10.1073/pnas.83.6.1670. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cathala G., Savouret J. F., Mendez B., West B. L., Karin M., Martial J. A., Baxter J. D. A method for isolation of intact, translationally active ribonucleic acid. DNA. 1983;2(4):329–335. doi: 10.1089/dna.1983.2.329. [DOI] [PubMed] [Google Scholar]
  8. Ciaglowski R. E., Snow J., Walz D. A. Isolation and amino acid sequence of bovine platelet factor 4. Arch Biochem Biophys. 1986 Oct;250(1):249–256. doi: 10.1016/0003-9861(86)90723-x. [DOI] [PubMed] [Google Scholar]
  9. Clore G. M., Appella E., Yamada M., Matsushima K., Gronenborn A. M. Determination of the secondary structure of interleukin-8 by nuclear magnetic resonance spectroscopy. J Biol Chem. 1989 Nov 15;264(32):18907–18911. [PubMed] [Google Scholar]
  10. Clore G. M., Appella E., Yamada M., Matsushima K., Gronenborn A. M. Three-dimensional structure of interleukin 8 in solution. Biochemistry. 1990 Feb 20;29(7):1689–1696. doi: 10.1021/bi00459a004. [DOI] [PubMed] [Google Scholar]
  11. Cochran B. H., Reffel A. C., Stiles C. D. Molecular cloning of gene sequences regulated by platelet-derived growth factor. Cell. 1983 Jul;33(3):939–947. doi: 10.1016/0092-8674(83)90037-5. [DOI] [PubMed] [Google Scholar]
  12. Davatelis G., Tekamp-Olson P., Wolpe S. D., Hermsen K., Luedke C., Gallegos C., Coit D., Merryweather J., Cerami A. Cloning and characterization of a cDNA for murine macrophage inflammatory protein (MIP), a novel monokine with inflammatory and chemokinetic properties. J Exp Med. 1988 Jun 1;167(6):1939–1944. doi: 10.1084/jem.167.6.1939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Deuel T. F., Keim P. S., Farmer M., Heinrikson R. L. Amino acid sequence of human platelet factor 4. Proc Natl Acad Sci U S A. 1977 Jun;74(6):2256–2258. doi: 10.1073/pnas.74.6.2256. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. DiLella A. G., Woo S. L. Cloning large segments of genomic DNA using cosmid vectors. Methods Enzymol. 1987;152:199–212. doi: 10.1016/0076-6879(87)52021-3. [DOI] [PubMed] [Google Scholar]
  15. Doi T., Greenberg S. M., Rosenberg R. D. Structure of the rat platelet factor 4 gene: a marker for megakaryocyte differentiation. Mol Cell Biol. 1987 Feb;7(2):898–904. doi: 10.1128/mcb.7.2.898. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Golds E. E., Mason P., Nyirkos P. Inflammatory cytokines induce synthesis and secretion of gro protein and a neutrophil chemotactic factor but not beta 2-microglobulin in human synovial cells and fibroblasts. Biochem J. 1989 Apr 15;259(2):585–588. doi: 10.1042/bj2590585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Green C. J., Charles R. S., Edwards B. F., Johnson P. H. Identification and characterization of PF4varl, a human gene variant of platelet factor 4. Mol Cell Biol. 1989 Apr;9(4):1445–1451. doi: 10.1128/mcb.9.4.1445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Griffin C. A., Emanuel B. S., LaRocco P., Schwartz E., Poncz M. Human platelet factor 4 gene is mapped to 4q12----q21. Cytogenet Cell Genet. 1987;45(2):67–69. doi: 10.1159/000132431. [DOI] [PubMed] [Google Scholar]
  19. Han J., Brown T., Beutler B. Endotoxin-responsive sequences control cachectin/tumor necrosis factor biosynthesis at the translational level. J Exp Med. 1990 Feb 1;171(2):465–475. doi: 10.1084/jem.171.2.465. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hermodson M., Schmer G., Kurachi K. Isolation, crystallization, and primary amino acid sequence of human platelet factor 4. J Biol Chem. 1977 Sep 25;252(18):6276–6279. [PubMed] [Google Scholar]
  21. Holt J. C., Harris M. E., Holt A. M., Lange E., Henschen A., Niewiarowski S. Characterization of human platelet basic protein, a precursor form of low-affinity platelet factor 4 and beta-thromboglobulin. Biochemistry. 1986 Apr 22;25(8):1988–1996. doi: 10.1021/bi00356a023. [DOI] [PubMed] [Google Scholar]
  22. Kozak M. An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs. Nucleic Acids Res. 1987 Oct 26;15(20):8125–8148. doi: 10.1093/nar/15.20.8125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Kruys V., Wathelet M., Poupart P., Contreras R., Fiers W., Content J., Huez G. The 3' untranslated region of the human interferon-beta mRNA has an inhibitory effect on translation. Proc Natl Acad Sci U S A. 1987 Sep;84(17):6030–6034. doi: 10.1073/pnas.84.17.6030. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Lipman D. J., Pearson W. R. Rapid and sensitive protein similarity searches. Science. 1985 Mar 22;227(4693):1435–1441. doi: 10.1126/science.2983426. [DOI] [PubMed] [Google Scholar]
  26. Luster A. D., Jhanwar S. C., Chaganti R. S., Kersey J. H., Ravetch J. V. Interferon-inducible gene maps to a chromosomal band associated with a (4;11) translocation in acute leukemia cells. Proc Natl Acad Sci U S A. 1987 May;84(9):2868–2871. doi: 10.1073/pnas.84.9.2868. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Luster A. D., Unkeless J. C., Ravetch J. V. Gamma-interferon transcriptionally regulates an early-response gene containing homology to platelet proteins. Nature. 1985 Jun 20;315(6021):672–676. doi: 10.1038/315672a0. [DOI] [PubMed] [Google Scholar]
  28. Matsushima K., Morishita K., Yoshimura T., Lavu S., Kobayashi Y., Lew W., Appella E., Kung H. F., Leonard E. J., Oppenheim J. J. Molecular cloning of a human monocyte-derived neutrophil chemotactic factor (MDNCF) and the induction of MDNCF mRNA by interleukin 1 and tumor necrosis factor. J Exp Med. 1988 Jun 1;167(6):1883–1893. doi: 10.1084/jem.167.6.1883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Modi W. S., Dean M., Seuanez H. N., Mukaida N., Matsushima K., O'Brien S. J. Monocyte-derived neutrophil chemotactic factor (MDNCF/IL-8) resides in a gene cluster along with several other members of the platelet factor 4 gene superfamily. Hum Genet. 1990 Jan;84(2):185–187. doi: 10.1007/BF00208938. [DOI] [PubMed] [Google Scholar]
  30. Myers E. W., Miller W. Optimal alignments in linear space. Comput Appl Biosci. 1988 Mar;4(1):11–17. doi: 10.1093/bioinformatics/4.1.11. [DOI] [PubMed] [Google Scholar]
  31. Nathan C. F. Secretory products of macrophages. J Clin Invest. 1987 Feb;79(2):319–326. doi: 10.1172/JCI112815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Needleman S. B., Wunsch C. D. A general method applicable to the search for similarities in the amino acid sequence of two proteins. J Mol Biol. 1970 Mar;48(3):443–453. doi: 10.1016/0022-2836(70)90057-4. [DOI] [PubMed] [Google Scholar]
  33. Oquendo P., Alberta J., Wen D. Z., Graycar J. L., Derynck R., Stiles C. D. The platelet-derived growth factor-inducible KC gene encodes a secretory protein related to platelet alpha-granule proteins. J Biol Chem. 1989 Mar 5;264(7):4133–4137. [PubMed] [Google Scholar]
  34. Perlman D., Halvorson H. O. A putative signal peptidase recognition site and sequence in eukaryotic and prokaryotic signal peptides. J Mol Biol. 1983 Jun 25;167(2):391–409. doi: 10.1016/s0022-2836(83)80341-6. [DOI] [PubMed] [Google Scholar]
  35. Poncz M., Surrey S., LaRocco P., Weiss M. J., Rappaport E. F., Conway T. M., Schwartz E. Cloning and characterization of platelet factor 4 cDNA derived from a human erythroleukemic cell line. Blood. 1987 Jan;69(1):219–223. [PubMed] [Google Scholar]
  36. Richmond A., Balentien E., Thomas H. G., Flaggs G., Barton D. E., Spiess J., Bordoni R., Francke U., Derynck R. Molecular characterization and chromosomal mapping of melanoma growth stimulatory activity, a growth factor structurally related to beta-thromboglobulin. EMBO J. 1988 Jul;7(7):2025–2033. doi: 10.1002/j.1460-2075.1988.tb03042.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Richmond A., Thomas H. G. Purification of melanoma growth stimulatory activity. J Cell Physiol. 1986 Dec;129(3):375–384. doi: 10.1002/jcp.1041290316. [DOI] [PubMed] [Google Scholar]
  38. 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]
  39. Schmid J., Weissmann C. Induction of mRNA for a serine protease and a beta-thromboglobulin-like protein in mitogen-stimulated human leukocytes. J Immunol. 1987 Jul 1;139(1):250–256. [PubMed] [Google Scholar]
  40. Schröder J. M., Mrowietz U., Morita E., Christophers E. Purification and partial biochemical characterization of a human monocyte-derived, neutrophil-activating peptide that lacks interleukin 1 activity. J Immunol. 1987 Nov 15;139(10):3474–3483. [PubMed] [Google Scholar]
  41. Shaw G., Kamen R. A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell. 1986 Aug 29;46(5):659–667. doi: 10.1016/0092-8674(86)90341-7. [DOI] [PubMed] [Google Scholar]
  42. Sobel E., Martinez H. M. A multiple sequence alignment program. Nucleic Acids Res. 1986 Jan 10;14(1):363–374. doi: 10.1093/nar/14.1.363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. St Charles R., Walz D. A., Edwards B. F. The three-dimensional structure of bovine platelet factor 4 at 3.0-A resolution. J Biol Chem. 1989 Feb 5;264(4):2092–2099. [PubMed] [Google Scholar]
  44. Sugano S., Stoeckle M. Y., Hanafusa H. Transformation by Rous sarcoma virus induces a novel gene with homology to a mitogenic platelet protein. Cell. 1987 May 8;49(3):321–328. doi: 10.1016/0092-8674(87)90284-4. [DOI] [PubMed] [Google Scholar]
  45. Sundström C., Nilsson K. Establishment and characterization of a human histiocytic lymphoma cell line (U-937). Int J Cancer. 1976 May 15;17(5):565–577. doi: 10.1002/ijc.2910170504. [DOI] [PubMed] [Google Scholar]
  46. Walz A., Peveri P., Aschauer H., Baggiolini M. Purification and amino acid sequencing of NAF, a novel neutrophil-activating factor produced by monocytes. Biochem Biophys Res Commun. 1987 Dec 16;149(2):755–761. doi: 10.1016/0006-291x(87)90432-3. [DOI] [PubMed] [Google Scholar]
  47. Watanabe K., Konishi K., Fujioka M., Kinoshita S., Nakagawa H. The neutrophil chemoattractant produced by the rat kidney epithelioid cell line NRK-52E is a protein related to the KC/gro protein. J Biol Chem. 1989 Nov 25;264(33):19559–19563. [PubMed] [Google Scholar]
  48. Wen D. Z., Rowland A., Derynck R. Expression and secretion of gro/MGSA by stimulated human endothelial cells. EMBO J. 1989 Jun;8(6):1761–1766. doi: 10.1002/j.1460-2075.1989.tb03569.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Wolpe S. D., Sherry B., Juers D., Davatelis G., Yurt R. W., Cerami A. Identification and characterization of macrophage inflammatory protein 2. Proc Natl Acad Sci U S A. 1989 Jan;86(2):612–616. doi: 10.1073/pnas.86.2.612. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Wood W. I., Gitschier J., Lasky L. A., Lawn R. M. Base composition-independent hybridization in tetramethylammonium chloride: a method for oligonucleotide screening of highly complex gene libraries. Proc Natl Acad Sci U S A. 1985 Mar;82(6):1585–1588. doi: 10.1073/pnas.82.6.1585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Yoshimura T., Matsushima K., Tanaka S., Robinson E. A., Appella E., Oppenheim J. J., Leonard E. J. Purification of a human monocyte-derived neutrophil chemotactic factor that has peptide sequence similarity to other host defense cytokines. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9233–9237. doi: 10.1073/pnas.84.24.9233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. von Heijne G. A new method for predicting signal sequence cleavage sites. Nucleic Acids Res. 1986 Jun 11;14(11):4683–4690. doi: 10.1093/nar/14.11.4683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. von Heijne G. How signal sequences maintain cleavage specificity. J Mol Biol. 1984 Feb 25;173(2):243–251. doi: 10.1016/0022-2836(84)90192-x. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES