Home LiteratureArticle Details
PMID: 8314845 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Identification of hyaluronic acid binding sites in the extracellular domain of CD44.

The Journal of cell biology ·Vol. 122 ·No. 1 ·1993-07-00 ·Pages 257-64

Peach RJ, Hollenbaugh D, Stamenkovic I, Aruffo A

Abstract

CD44 is a polymorphic glycoprotein expressed on the surface of many tissues and cell lines which has been implicated in a number of cellular functions including lymphocyte homing to mucosal lymphoid tissue (Peyers patches), leukocyte activation, lymphopoiesis, and tumor metastasis. The predominant isoform found on human leukocytes, CD44H, is a receptor for hyaluronic acid. Because of the prominent role CD44 plays in diverse biological processes, we set out to identify the hyaluronic acid binding site(s) in the extracellular domain of CD44H. Using truncation and site-directed mutagenesis we identified two regions containing clusters of conserved basic residues which are important in hyaluronic acid binding. One of these regions is situated near the NH2 terminus and is homologous to other hyaluronic acid binding proteins including cartilage link protein. The other more membrane proximal region lies outside the link protein homologous domain. Mutagenesis of basic residues within these regions established their role as determinants in hyaluronic acid binding. Mutation of Arg 41, a position where a basic residue is conserved in all hyaluronic acid binding proteins, completely abolished binding suggesting that this residue plays a critical role in hyaluronic acid binding.

MeSH Terms
Amino Acid Sequence Animals Antibodies, Monoclonal/metabolism Antigens, CD/genetics,metabolism Base Sequence Binding Sites Binding Sites, Antibody Cell Line Cell Membrane/metabolism Humans Hyaluronic Acid/metabolism Kinetics Molecular Sequence Data Mutagenesis, Site-Directed Oligodeoxyribonucleotides Receptors, Lymphocyte Homing/genetics,metabolism Recombinant Proteins/metabolism Transfection
Chemicals
Antibodies, Monoclonal Antigens, CD Oligodeoxyribonucleotides Receptors, Lymphocyte Homing Recombinant Proteins Hyaluronic Acid
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Peach R J
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121.
Hollenbaugh D
Stamenkovic I
Aruffo A
References (49)
49 references, click to expand
  1. Murine cell surface glycoproteins. Characterization of a major component of 80,000 daltons as a polymorphic differentiation antigen of mesenchymal cells.
    J Biol Chem. 1981 Jul 10;256(13):7023-7 PMID: 6787057
  2. The hyaluronate receptor is a member of the CD44 (H-CAM) family of cell surface glycoproteins.
    J Cell Biol. 1990 Dec;111(6 Pt 1):2765-74 PMID: 1703543
  3. The hematopoietic and epithelial forms of CD44 are distinct polypeptides with different adhesion potentials for hyaluronate-bearing cells.
    EMBO J. 1991 Feb;10(2):343-8 PMID: 1991450
  4. Glycosaminoglycans: molecular properties, protein interactions, and role in physiological processes.
    Physiol Rev. 1991 Apr;71(2):481-539 PMID: 2006221
  5. Human keratinocytes express a new CD44 core protein (CD44E) as a heparan-sulfate intrinsic membrane proteoglycan with additional exons.
    J Cell Biol. 1991 Apr;113(1):207-21 PMID: 2007624
  6. A new variant of glycoprotein CD44 confers metastatic potential to rat carcinoma cells.
    Cell. 1991 Apr 5;65(1):13-24 PMID: 1707342
  7. Somatic cell mutants distinguish CD44 expression and hyaluronic acid binding.
    Immunogenetics. 1991;33(5-6):392-5 PMID: 2050392
  8. Distinct effects of two CD44 isoforms on tumor growth in vivo.
    J Exp Med. 1991 Oct 1;174(4):859-66 PMID: 1919439
  9. Expression of CD44 is repressed in neuroblastoma cells.
    Mol Cell Biol. 1991 Nov;11(11):5446-53 PMID: 1922057
  10. Sequence of the bovine CD44 cDNA: comparison with human and mouse sequences.
    Mol Immunol. 1991 Oct;28(10):1131-5 PMID: 1922105
  11. Variations in the cytoskeletal interaction and posttranslational modification of the CD44 homing receptor in macrophages.
    J Cell Biol. 1991 Dec;115(5):1283-92 PMID: 1955476
  12. A novel secretory tumor necrosis factor-inducible protein (TSG-6) is a member of the family of hyaluronate binding proteins, closely related to the adhesion receptor CD44.
    J Cell Biol. 1992 Jan;116(2):545-57 PMID: 1730767
  13. Lymphocyte CD44 binds the COOH-terminal heparin-binding domain of fibronectin.
    J Cell Biol. 1992 Feb;116(3):817-25 PMID: 1730778
  14. Requirements for hyaluronic acid binding by CD44: a role for the cytoplasmic domain and activation by antibody.
    J Exp Med. 1992 Jan 1;175(1):257-66 PMID: 1730918
  15. Multiple variants of the human lymphocyte homing receptor CD44 generated by insertions at a single site in the extracellular domain.
    J Biol Chem. 1992 Mar 5;267(7):4732-9 PMID: 1537855
  16. Granule membrane protein 140 (GMP140) binds to carcinomas and carcinoma-derived cell lines.
    Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2292-6 PMID: 1372439
  17. Hyaluronate binding properties of versican.
    J Biol Chem. 1992 May 15;267(14):10003-10 PMID: 1577773
  18. CD44H regulates tumor cell migration on hyaluronate-coated substrate.
    J Cell Biol. 1992 Aug;118(4):971-7 PMID: 1380003
  19. Genomic structure of DNA encoding the lymphocyte homing receptor CD44 reveals at least 12 alternatively spliced exons.
    Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12160-4 PMID: 1465456
  20. Molecular isoforms of murine CD44 and evidence that the membrane proximal domain is not critical for hyaluronate recognition.
    J Cell Biol. 1992 Dec;119(6):1711-9 PMID: 1469058
  21. Structural heterogeneity of human Pgp-1 and its relationship with p85.
    Immunogenetics. 1988;27(6):460-4 PMID: 3286493
  22. Effects of detergent solubilization on the hyaluronate-binding protein from membranes of simian virus 40-transformed 3T3 cells.
    J Biol Chem. 1983 Jul 10;258(13):8086-91 PMID: 6190806
  23. Specific chemical modifications of link protein and their effect on binding to hyaluronate and cartilage proteoglycan.
    Biochim Biophys Acta. 1986 Mar 19;881(1):22-9 PMID: 3081049
  24. Link protein cDNA sequence reveals a tandemly repeated protein structure.
    Proc Natl Acad Sci U S A. 1986 Jun;83(11):3761-5 PMID: 3459153
  25. Complete amino acid sequence of chicken cartilage link protein deduced from cDNA clones.
    Proc Natl Acad Sci U S A. 1986 Jun;83(11):3766-70 PMID: 3459154
  26. A lymphoid cell surface glycoprotein involved in endothelial cell recognition and lymphocyte homing in man.
    Eur J Immunol. 1986 Oct;16(10):1195-202 PMID: 2429846
  27. Lymphocyte recognition of high endothelium: antibodies to distinct epitopes of an 85-95-kD glycoprotein antigen differentially inhibit lymphocyte binding to lymph node, mucosal, or synovial endothelial cells.
    J Cell Biol. 1987 Aug;105(2):983-90 PMID: 2442176
  28. The tandemly repeated sequences of cartilage link protein contain the sites for interaction with hyaluronic acid.
    J Cell Biol. 1987 Nov;105(5):2403-8 PMID: 2445761
  29. Molecular cloning of a CD28 cDNA by a high-efficiency COS cell expression system.
    Proc Natl Acad Sci U S A. 1987 Dec;84(23):8573-7 PMID: 2825196
  30. Complete primary structure of the rat cartilage proteoglycan core protein deduced from cDNA clones.
    J Biol Chem. 1987 Dec 25;262(36):17757-67 PMID: 3693370
  31. Characterization of the class III collagen receptor, a phosphorylated, transmembrane glycoprotein expressed in nucleated human cells.
    J Biol Chem. 1988 Mar 25;263(9):4193-201 PMID: 2831221
  32. A lymphocyte molecule implicated in lymph node homing is a member of the cartilage link protein family.
    Cell. 1989 Mar 24;56(6):1057-62 PMID: 2466575
  33. A human lymphocyte homing receptor, the hermes antigen, is related to cartilage proteoglycan core and link proteins.
    Cell. 1989 Mar 24;56(6):1063-72 PMID: 2466576
  34. Isolation and DNA sequence of a cDNA clone encoding a lymphocyte adhesion receptor for high endothelium.
    Proc Natl Acad Sci U S A. 1989 Jun;86(12):4659-63 PMID: 2471974
  35. Site-directed mutagenesis by overlap extension using the polymerase chain reaction.
    Gene. 1989 Apr 15;77(1):51-9 PMID: 2744487
  36. CD44 contributes to T cell activation.
    J Immunol. 1989 Aug 1;143(3):798-801 PMID: 2568380
  37. Dual role of the CD44 molecule in T cell adhesion and activation.
    J Immunol. 1989 Oct 15;143(8):2457-63 PMID: 2677141
  38. Cartilage proteoglycans. Structure and heterogeneity of the protein core and the effects of specific protein modifications on the binding to hyaluronate.
    Biochem J. 1976 Jul 1;157(1):127-43 PMID: 134698
  39. Monoclonal antibody to a human brain-granulocyte-T lymphocyte antigen probably homologous to the W 3/13 antigen of the rat.
    Eur J Immunol. 1980 Oct;10(10):745-9 PMID: 6968681
  40. Molecular cloning and expression of Pgp-1. The mouse homolog of the human H-CAM (Hermes) lymphocyte homing receptor.
    J Immunol. 1989 Nov 15;143(10):3390-5 PMID: 2681416
  41. Isolation of mouse CD44 cDNA: structural features are distinct from the primate cDNA.
    Proc Natl Acad Sci U S A. 1989 Nov;86(21):8521-5 PMID: 2682651
  42. Antibodies against the CD44 p80, lymphocyte homing receptor molecule augment human peripheral blood T cell activation.
    J Immunol. 1990 Jan 1;144(1):7-15 PMID: 1967267
  43. CD44--a molecule involved in leukocyte adherence and T-cell activation.
    Immunol Today. 1989 Dec;10(12):423-8 PMID: 2695102
  44. Monoclonal antibodies to Pgp-1/CD44 block lympho-hemopoiesis in long-term bone marrow cultures.
    J Exp Med. 1990 Feb 1;171(2):477-88 PMID: 2406365
  45. Hyaluronate can function as a cell adhesion molecule and CD44 participates in hyaluronate recognition.
    J Exp Med. 1990 Jul 1;172(1):69-75 PMID: 2193100
  46. CD44 is the principal cell surface receptor for hyaluronate.
    Cell. 1990 Jun 29;61(7):1303-13 PMID: 1694723
  47. LFA-3, CD44, and CD45: physiologic triggers of human monocyte TNF and IL-1 release.
    Science. 1990 Sep 14;249(4974):1295-7 PMID: 1697984
  48. Confirmation by peptide sequence and co-expression on various cell types of the identity of CD44 and P85 glycoprotein.
    Mol Immunol. 1990 Oct;27(10):947-55 PMID: 2233756
  49. Genetic characterization of a polymorphic murine cell-surface glycoprotein.
    Immunogenetics. 1982 Mar;15(3):313-20 PMID: 7068175
Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.122.1.257
Published
1993-07-00
Pages
257-64
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2119597
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.122.1.257 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2