Search tips
Search criteria 


Logo of jcinvestThe Journal of Clinical Investigation
J Clin Invest. 1988 June; 81(6): 1993–1998.
PMCID: PMC442653

Chromosomal localization of the genes for the vitronectin and fibronectin receptors alpha subunits and for platelet glycoproteins IIb and IIIa.


The integrins, a family of related membrane receptors involved in cell-cell and cell-matrix interactions, are heterodimeric complexes of alpha and beta subunits. To begin to understand the evolution of these complexes, we studied the genomic organization of several alpha and beta integrin subunits. Using both somatic cell hybrids and an in situ hybridization technique, we have determined the chromosomal location of the genes for the alpha subunits of the vitronectin receptor (VNR alpha), the fibronectin receptor (FNR alpha), and for the alpha subunit of the platelet glycoprotein IIb/IIIa complex, GPIIb. In addition, we have determined the chromosomal location of the gene for the beta subunit of the GPIIb/IIIa heterodimer, GPIIIa. Our studies indicate that the alpha subunits do not localize to a single locus, but that each is found on a different chromosome. The gene for VNR alpha is located on chromosome 2, the gene for FNR alpha is on chromosome 12q11----13, and the gene for GPIIb is on chromosome 17q21----23. In contrast to the chromosomal dispersion of the alpha subunits, the genes for GPIIb and GPIIIa are physically close, with the gene for GPIIIa also located on chromosome 17q21----23. These studies indicate that the genes for the alpha subunits of the integrin family have been dispersed during evolution while GPIIb and GPIIIa are in close physical proximity. This physical proximity of GPIIb and GPIIIa may be involved in the concurrent expression of these proteins by megakaryocytes, and may result in linkage disequilibrium between these two genes, which would limit the use of restriction length polymorphisms in linkage studies of GPIIb/IIIa abnormalities in small kindreds.

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 (1009K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Hynes RO. Integrins: a family of cell surface receptors. Cell. 1987 Feb 27;48(4):549–554. [PubMed]
  • Jennings LK, Phillips DR. Purification of glycoproteins IIb and III from human platelet plasma membranes and characterization of a calcium-dependent glycoprotein IIb-III complex. J Biol Chem. 1982 Sep 10;257(17):10458–10466. [PubMed]
  • Springer TA. The LFA-1, Mac-1 glycoprotein family and its deficiency in an inherited disease. Fed Proc. 1985 Jul;44(10):2660–2663. [PubMed]
  • Anderson DC, Springer TA. Leukocyte adhesion deficiency: an inherited defect in the Mac-1, LFA-1, and p150,95 glycoproteins. Annu Rev Med. 1987;38:175–194. [PubMed]
  • Giancotti FG, Tarone G, Knudsen K, Damsky C, Comoglio PM. Cleavage of a 135 kD cell surface glycoprotein correlates with loss of fibroblast adhesion to fibronectin. Exp Cell Res. 1985 Jan;156(1):182–190. [PubMed]
  • Pytela R, Pierschbacher MD, Ruoslahti E. Identification and isolation of a 140 kd cell surface glycoprotein with properties expected of a fibronectin receptor. Cell. 1985 Jan;40(1):191–198. [PubMed]
  • Tamkun JW, DeSimone DW, Fonda D, Patel RS, Buck C, Horwitz AF, Hynes RO. Structure of integrin, a glycoprotein involved in the transmembrane linkage between fibronectin and actin. Cell. 1986 Jul 18;46(2):271–282. [PubMed]
  • Argraves WS, Pytela R, Suzuki S, Millán JL, Pierschbacher MD, Ruoslahti E. cDNA sequences from the alpha subunit of the fibronectin receptor predict a transmembrane domain and a short cytoplasmic peptide. J Biol Chem. 1986 Oct 5;261(28):12922–12924. [PubMed]
  • Suzuki S, Argraves WS, Pytela R, Arai H, Krusius T, Pierschbacher MD, Ruoslahti E. cDNA and amino acid sequences of the cell adhesion protein receptor recognizing vitronectin reveal a transmembrane domain and homologies with other adhesion protein receptors. Proc Natl Acad Sci U S A. 1986 Nov;83(22):8614–8618. [PubMed]
  • Fitzgerald LA, Steiner B, Rall SC, Jr, Lo SS, Phillips DR. Protein sequence of endothelial glycoprotein IIIa derived from a cDNA clone. Identity with platelet glycoprotein IIIa and similarity to "integrin". J Biol Chem. 1987 Mar 25;262(9):3936–3939. [PubMed]
  • Poncz M, Eisman R, Heidenreich R, Silver SM, Vilaire G, Surrey S, Schwartz E, Bennett JS. Structure of the platelet membrane glycoprotein IIb. Homology to the alpha subunits of the vitronectin and fibronectin membrane receptors. J Biol Chem. 1987 Jun 25;262(18):8476–8482. [PubMed]
  • Kishimoto TK, O'Connor K, Lee A, Roberts TM, Springer TA. Cloning of the beta subunit of the leukocyte adhesion proteins: homology to an extracellular matrix receptor defines a novel supergene family. Cell. 1987 Feb 27;48(4):681–690. [PubMed]
  • Fitzgerald LA, Poncz M, Steiner B, Rall SC, Jr, Bennett JS, Phillips DR. Comparison of cDNA-derived protein sequences of the human fibronectin and vitronectin receptor alpha-subunits and platelet glycoprotein IIb. Biochemistry. 1987 Dec 15;26(25):8158–8165. [PubMed]
  • Zimrin AB, Eisman R, Vilaire G, Schwartz E, Bennett JS, Poncz M. Structure of platelet glycoprotein IIIa. A common subunit for two different membrane receptors. J Clin Invest. 1988 May;81(5):1470–1475. [PMC free article] [PubMed]
  • Birnboim HC, Doly J. A rapid alkaline extraction procedure for screening recombinant plasmid DNA. Nucleic Acids Res. 1979 Nov 24;7(6):1513–1523. [PMC free article] [PubMed]
  • Poncz M, Solowiejczyk D, Ballantine M, Schwartz E, Surrey S. "Nonrandom" DNA sequence analysis in bacteriophage M13 by the dideoxy chain-termination method. Proc Natl Acad Sci U S A. 1982 Jul;79(14):4298–4302. [PubMed]
  • Nussbaum RL, Crowder WE, Nyhan WL, Caskey CT. A three-allele restriction-fragment-length polymorphism at the hypoxanthine phosphoribosyltransferase locus in man. Proc Natl Acad Sci U S A. 1983 Jul;80(13):4035–4039. [PubMed]
  • Seabright M. A rapid banding technique for human chromosomes. Lancet. 1971 Oct 30;2(7731):971–972. [PubMed]
  • Patel PI, Nussbaum RL, gramson PE, Ledbetter DH, Caskey CT, Chinault AC. Organization of the HPRT gene and related sequences in the human genome. Somat Cell Mol Genet. 1984 Sep;10(5):483–493. [PubMed]
  • Ledbetter DH, Ledbetter SA, Nussbaum RL. Implications of fragile X expression in normal males for the nature of the mutation. Nature. 1986 Nov 13;324(6093):161–163. [PubMed]
  • Chan L, VanTuinen P, Ledbetter DH, Daiger SP, Gotto AM, Jr, Chen SH. The human apolipoprotein B-100 gene: a highly polymorphic gene that maps to the short arm of chromosome 2. Biochem Biophys Res Commun. 1985 Nov 27;133(1):248–255. [PubMed]
  • Law ML, Cai GY, Lin FK, Wei Q, Huang SZ, Hartz JH, Morse H, Lin CH, Jones C, Kao FT. Chromosomal assignment of the human erythropoietin gene and its DNA polymorphism. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6920–6924. [PubMed]
  • Nussbaum RL, Walmsley RM, Lesko JG, Airhart SD, Ledbetter DH. Thymidylate synthase-deficient Chinese hamster cells: a selection system for human chromosome 18 and experimental system for the study of thymidylate synthase regulation and fragile X expression. Am J Hum Genet. 1985 Nov;37(6):1192–1205. [PubMed]
  • Southern EM. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. [PubMed]
  • Feinberg AP, Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. [PubMed]
  • Harper ME, Saunders GF. Localization of single copy DNA sequences of G-banded human chromosomes by in situ hybridization. Chromosoma. 1981;83(3):431–439. [PubMed]
  • Cannizzaro LA, Emanuel BS. An improved method for G-banding chromosomes after in situ hybridization. Cytogenet Cell Genet. 1984;38(4):308–309. [PubMed]
  • van Tuinen P, Johnson KR, Ledbetter SA, Nussbaum RL, Rovera G, Ledbetter DH. Localization of myeloperoxidase to the long arm of human chromosome 17: relationship to the 15; 17 translocation of acute promyelocytic leukemia. Oncogene. 1987;1(3):319–322. [PubMed]
  • Bray PF, Rosa JP, Johnston GI, Shiu DT, Cook RG, Lau C, Kan YW, McEver RP, Shuman MA. Platelet glycoprotein IIb. Chromosomal localization and tissue expression. J Clin Invest. 1987 Dec;80(6):1812–1817. [PMC free article] [PubMed]
  • Marlin SD, Morton CC, Anderson DC, Springer TA. LFA-1 immunodeficiency disease. Definition of the genetic defect and chromosomal mapping of alpha and beta subunits of the lymphocyte function-associated antigen 1 (LFA-1) by complementation in hybrid cells. J Exp Med. 1986 Sep 1;164(3):855–867. [PMC free article] [PubMed]
  • Peters PM, Kamarck ME, Hemler ME, Strominger JL, Ruddle FH. Genetic and biochemical characterization of human lymphocyte cell surface antigens. The A-1A5 and A-3A4 determinants. J Exp Med. 1984 May 1;159(5):1441–1454. [PMC free article] [PubMed]
  • Tamkun JW, DeSimone DW, Fonda D, Patel RS, Buck C, Horwitz AF, Hynes RO. Structure of integrin, a glycoprotein involved in the transmembrane linkage between fibronectin and actin. Cell. 1986 Jul 18;46(2):271–282. [PubMed]
  • Rabellino EM, Levene RB, Leung LL, Nachman RL. Human megakaryocytes. II. Expression of platelet proteins in early marrow megakaryocytes. J Exp Med. 1981 Jul 1;154(1):88–100. [PMC free article] [PubMed]
  • Bennett JS, Hoxie JA, Leitman SF, Vilaire G, Cines DB. Inhibition of fibrinogen binding to stimulated human platelets by a monoclonal antibody. Proc Natl Acad Sci U S A. 1983 May;80(9):2417–2421. [PubMed]
  • Pytela R, Pierschbacher MD, Ginsberg MH, Plow EF, Ruoslahti E. Platelet membrane glycoprotein IIb/IIIa: member of a family of Arg-Gly-Asp--specific adhesion receptors. Science. 1986 Mar 28;231(4745):1559–1562. [PubMed]
  • Plow EF, McEver RP, Coller BS, Woods VL, Jr, Marguerie GA, Ginsberg MH. Related binding mechanisms for fibrinogen, fibronectin, von Willebrand factor, and thrombospondin on thrombin-stimulated human platelets. Blood. 1985 Sep;66(3):724–727. [PubMed]
  • Nurden AT, Caen JP. The different glycoprotein abnormalities in thrombasthenic and Bernard-Soulier platelets. Semin Hematol. 1979 Jul;16(3):234–250. [PubMed]
  • Johansson S, Forsberg E, Lundgren B. Comparison of fibronectin receptors from rat hepatocytes and fibroblasts. J Biol Chem. 1987 Jun 5;262(16):7819–7824. [PubMed]
  • Giltay JC, Leeksma OC, Breederveld C, van Mourik JA. Normal synthesis and expression of endothelial IIb/IIIa in Glanzmann's thrombasthenia. Blood. 1987 Mar;69(3):809–812. [PubMed]
  • Kishimoto TK, Hollander N, Roberts TM, Anderson DC, Springer TA. Heterogeneous mutations in the beta subunit common to the LFA-1, Mac-1, and p150,95 glycoproteins cause leukocyte adhesion deficiency. Cell. 1987 Jul 17;50(2):193–202. [PubMed]

Articles from The Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation