• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. May 1, 1993; 90(9): 3943–3947.

Vascular cell adhesion molecule 1: contrasting transcriptional control mechanisms in muscle and endothelium.


Interaction between vascular cell adhesion molecule 1 (VCAM-1), which appears on the surface of endothelial cells in response to inflammation, and its integrin counter receptor, alpha 4 beta 1, on immune cells is responsible for targeting these immune cells to cytokine-stimulated endothelium. In addition to its role in the immune system, VCAM-1 is also expressed in a developmentally specific pattern on differentiating skeletal muscle, where it mediates cell-cell interactions important for myogenesis through interaction with alpha 4 beta 1. In contrast to endothelium, there is high basal expression of VCAM-1 in skeletal muscle cells and the expression is not cytokine-responsive. Here, we examine the molecular basis for these contrasting patterns of expression in muscle and endothelium, using VCAM-1 promoter constructs in a series of transfection assays. In endothelial cells, octamer binding sites act as silencers that prevent VCAM-1 expression in unstimulated cells. Tumor necrosis factor alpha overcomes the negative effects of these octamers and activates the promoter through two adjacent NF-kappa B binding sites. In muscle cells, a position-specific enhancer located between bp -21 and -5 overrides the effect of other promoter elements, resulting in constitutive VCAM-1 expression. A nuclear protein binds the position-specific enhancer in muscle but not endothelial cells; thus the pattern of expression of this protein could control enhancer activity.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.3M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Elices MJ, Osborn L, Takada Y, Crouse C, Luhowskyj S, Hemler ME, Lobb RR. VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/fibronectin binding site. Cell. 1990 Feb 23;60(4):577–584. [PubMed]
  • Osborn L, Hession C, Tizard R, Vassallo C, Luhowskyj S, Chi-Rosso G, Lobb R. Direct expression cloning of vascular cell adhesion molecule 1, a cytokine-induced endothelial protein that binds to lymphocytes. Cell. 1989 Dec 22;59(6):1203–1211. [PubMed]
  • Rice GE, Munro JM, Corless C, Bevilacqua MP. Vascular and nonvascular expression of INCAM-110. A target for mononuclear leukocyte adhesion in normal and inflamed human tissues. Am J Pathol. 1991 Feb;138(2):385–393. [PMC free article] [PubMed]
  • Hemler ME, Huang C, Schwarz L. The VLA protein family. Characterization of five distinct cell surface heterodimers each with a common 130,000 molecular weight beta subunit. J Biol Chem. 1987 Mar 5;262(7):3300–3309. [PubMed]
  • Erle DJ, Rüegg C, Sheppard D, Pytela R. Complete amino acid sequence of an integrin beta subunit (beta 7) identified in leukocytes. J Biol Chem. 1991 Jun 15;266(17):11009–11016. [PubMed]
  • Freedman AS, Munro JM, Rice GE, Bevilacqua MP, Morimoto C, McIntyre BW, Rhynhart K, Pober JS, Nadler LM. Adhesion of human B cells to germinal centers in vitro involves VLA-4 and INCAM-110. Science. 1990 Aug 31;249(4972):1030–1033. [PubMed]
  • Miyake K, Weissman IL, Greenberger JS, Kincade PW. Evidence for a role of the integrin VLA-4 in lympho-hemopoiesis. J Exp Med. 1991 Mar 1;173(3):599–607. [PMC free article] [PubMed]
  • Scheeren RA, Koopman G, Van der Baan S, Meijer CJ, Pals ST. Adhesion receptors involved in clustering of blood dendritic cells and T lymphocytes. Eur J Immunol. 1991 May;21(5):1101–1105. [PubMed]
  • Rice GE, Munro JM, Bevilacqua MP. Inducible cell adhesion molecule 110 (INCAM-110) is an endothelial receptor for lymphocytes. A CD11/CD18-independent adhesion mechanism. J Exp Med. 1990 Apr 1;171(4):1369–1374. [PMC free article] [PubMed]
  • Carlos T, Kovach N, Schwartz B, Rosa M, Newman B, Wayner E, Benjamin C, Osborn L, Lobb R, Harlan J. Human monocytes bind to two cytokine-induced adhesive ligands on cultured human endothelial cells: endothelial-leukocyte adhesion molecule-1 and vascular cell adhesion molecule-1. Blood. 1991 May 15;77(10):2266–2271. [PubMed]
  • Shimizu Y, Newman W, Gopal TV, Horgan KJ, Graber N, Beall LD, van Seventer GA, Shaw S. Four molecular pathways of T cell adhesion to endothelial cells: roles of LFA-1, VCAM-1, and ELAM-1 and changes in pathway hierarchy under different activation conditions. J Cell Biol. 1991 Jun;113(5):1203–1212. [PMC free article] [PubMed]
  • Rüegg C, Postigo AA, Sikorski EE, Butcher EC, Pytela R, Erle DJ. Role of integrin alpha 4 beta 7/alpha 4 beta P in lymphocyte adherence to fibronectin and VCAM-1 and in homotypic cell clustering. J Cell Biol. 1992 Apr;117(1):179–189. [PMC free article] [PubMed]
  • Rosen GD, Sanes JR, LaChance R, Cunningham JM, Roman J, Dean DC. Roles for the integrin VLA-4 and its counter receptor VCAM-1 in myogenesis. Cell. 1992 Jun 26;69(7):1107–1119. [PubMed]
  • Iademarco MF, McQuillan JJ, Rosen GD, Dean DC. Characterization of the promoter for vascular cell adhesion molecule-1 (VCAM-1). J Biol Chem. 1992 Aug 15;267(23):16323–16329. [PubMed]
  • Yaffe D. Retention of differentiation potentialities during prolonged cultivation of myogenic cells. Proc Natl Acad Sci U S A. 1968 Oct;61(2):477–483. [PMC free article] [PubMed]
  • Birkenmeier TM, McQuillan JJ, Boedeker ED, Argraves WS, Ruoslahti E, Dean DC. The alpha 5 beta 1 fibronectin receptor. Characterization of the alpha 5 gene promoter. J Biol Chem. 1991 Oct 25;266(30):20544–20549. [PubMed]
  • McBurney MW, Rogers BJ. Isolation of male embryonal carcinoma cells and their chromosome replication patterns. Dev Biol. 1982 Feb;89(2):503–508. [PubMed]
  • Rosen GD, Birkenmeier TM, Dean DC. Characterization of the alpha 4 integrin gene promoter. Proc Natl Acad Sci U S A. 1991 May 15;88(10):4094–4098. [PMC free article] [PubMed]
  • Miyake K, Medina K, Ishihara K, Kimoto M, Auerbach R, Kincade PW. A VCAM-like adhesion molecule on murine bone marrow stromal cells mediates binding of lymphocyte precursors in culture. J Cell Biol. 1991 Aug;114(3):557–565. [PMC free article] [PubMed]
  • Weintraub SJ, Dean DC. Interaction of a common factor with ATF, Sp1, or TATAA promoter elements is required for these sequences to mediate transactivation by the adenoviral oncogene E1a. Mol Cell Biol. 1992 Feb;12(2):512–517. [PMC free article] [PubMed]
  • Kemler I, Bucher E, Seipel K, Müller-Immerglück MM, Schaffner W. Promoters with the octamer DNA motif (ATGCAAAT) can be ubiquitous or cell type-specific depending on binding affinity of the octamer site and Oct-factor concentration. Nucleic Acids Res. 1991 Jan 25;19(2):237–242. [PMC free article] [PubMed]
  • Dean DC, McQuillan JJ, Weintraub S. Serum stimulation of fibronectin gene expression appears to result from rapid serum-induced binding of nuclear proteins to a cAMP response element. J Biol Chem. 1990 Feb 25;265(6):3522–3527. [PubMed]
  • Haggarty A, Camato R, Paterno G, Cohen L, Hiscott J, Skup D. A developmentally regulated octamer-binding activity in embryonal carcinoma cells which represses beta-interferon expression. Cell Growth Differ. 1991 Oct;2(10):503–510. [PubMed]
  • Dean DC, Bowlus CL, Bourgeois S. Cloning and analysis of the promotor region of the human fibronectin gene. Proc Natl Acad Sci U S A. 1987 Apr;84(7):1876–1880. [PMC free article] [PubMed]
  • Tanaka M, Herr W. Differential transcriptional activation by Oct-1 and Oct-2: interdependent activation domains induce Oct-2 phosphorylation. Cell. 1990 Feb 9;60(3):375–386. [PubMed]
  • Dent CL, Lillycrop KA, Estridge JK, Thomas NS, Latchman DS. The B-cell and neuronal forms of the octamer-binding protein Oct-2 differ in DNA-binding specificity and functional activity. Mol Cell Biol. 1991 Aug;11(8):3925–3930. [PMC free article] [PubMed]
  • Smale ST, Baltimore D. The "initiator" as a transcription control element. Cell. 1989 Apr 7;57(1):103–113. [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...