Pathway Map Details

Cell adhesion_Cell-matrix glycoconjugates



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Object list (links open in MetaCore):

Leukocyte elastase, Aggrecan, L-selectin, chondroitin 4'-sulfate, Galectin-3, Laminin 1, BCAN, NCAM1, ITIH2, ITIH3, CD44, MMP-9, ITIH, MMP-1, Lymphotactin, Fibulin-1, Neurocan, Plasmin, Tenascin-C, Hyaluronic acid, E-selectin, Fibulin-2, ECM1, Tenascin-R, Stromelysin-1, CEACAM5, Elastin, CCL5, LYVE-1, CCL8, Versican, CRTL1, CSPG4 (NG2), MUC1, TIMP2, A1M, alpha-3/beta-1 integrin, Galectin-4

Description:

Cell- matrix glycoconjugates

Extracellular matrix (ECM) is composed of several macromolecules bound together in a complex network. This structure allows cells to adhere, migrate and interact. Hyaluronic acid, a glycosaminoglycan, is a major component of ECM. Hyaluronic acid -binding proteins such as hyaluronic acid receptor LYVE-1, CD44, cartilage link protein CRTL1, Aggrecan, Brevican ( BCAN ) , Neurocan and Versican, are implicated in cell-matrix interactions and in structurization of the ECM via stabilizing large macromolecular aggregates. They also play an important role in tumor metastasis and cell motility [1], [2], [3], [4].

Aggrecan, Versican, Neurocan, and BCAN are chondroitin sulfate proteoglycans of the ECM. Their interactions with cell surface proteins, as well as with chemokines such as CCL8, CCL5 and Lymphotactin, play important role in cell adhesion [5].

Fibulins are another family of the ECM proteins. Fibulins cross-link hyaluronan-proteoglycan complexes that play an essential role in supramolecular organization of cartilaginous and other extracellular matrices [6].

Tenascins are a family of large oligomeric ECM glycoproteins. They all modulate cell-matrix interactions and define the state of matrix attachment that promotes cell motility [7].

Galectins are a family of beta-galactoside-binding proteins implicated in modulating cell-cell and cell-matrix interactions. Galectins exist in intracellular and extracellular milieu. In extracellular space, they link with beta-galactoside containing glycoconjugates of the ECM and cell surface adhesion molecules that regulate cell adhesion and differentiation [8], [9], [10].

ECM remodeling is regulated by a huge number of proteinases and their inhibitors. Alpha-1-microglobulin ( A1M ) is a serine-proteinase inhibitor. It forms complexes with one or two heavy chains, Inter-alpha (globulin) inhibitors H1, H2 and H3 ( ITIH, ITIH2 and ITIH3 ) [11]. The heavy chains are linked to hyaluronic acid, and this attachment greatly improves ECM stability [1]. A1M exerts an inhibitory activity towards Elastase-2 and Plasmin and it thus suspected of playing a key role in ECM biology [12].

Plasmin takes part in the processing of the matrix metallopreoteinases (MMPs), such as MMP-1. It also cleaves ECM proteins [13], [14]. Plasmin, MMPs (such as MMP-1, MMP-9 and Stromelysin-1 ), and inhibitors of MMPs (such as TIMP2) directly participate in regulation of cell adhesion, migration, and ECM remodeling [15], [16].

References:

  1. Bost F, Diarra-Mehrpour M, Martin JP
    Inter-alpha-trypsin inhibitor proteoglycan family--a group of proteins binding and stabilizing the extracellular matrix. European journal of biochemistry / FEBS 1998 Mar 15;252(3):339-46
  2. Politz O, Gratchev A, McCourt PA, Schledzewski K, Guillot P, Johansson S, Svineng G, Franke P, Kannicht C, Kzhyshkowska J, Longati P, Velten FW, Goerdt S
    Stabilin-1 and -2 constitute a novel family of fasciclin-like hyaluronan receptor homologues. The Biochemical journal 2002 Feb 15;362(Pt 1):155-64
  3. Jackson DG
    The lymphatics revisited: new perspectives from the hyaluronan receptor LYVE-1. Trends in cardiovascular medicine 2003 Jan;13(1):1-7
  4. Seyfried NT, McVey GF, Almond A, Mahoney DJ, Dudhia J, Day AJ
    Expression and purification of functionally active hyaluronan-binding domains from human cartilage link protein, aggrecan and versican: formation of ternary complexes with defined hyaluronan oligosaccharides. The Journal of biological chemistry 2005 Feb 18;280(7):5435-48
  5. Hirose J, Kawashima H, Yoshie O, Tashiro K, Miyasaka M
    Versican interacts with chemokines and modulates cellular responses. The Journal of biological chemistry 2001 Feb 16;276(7):5228-34
  6. Olin AI, Morgelin M, Sasaki T, Timpl R, Heinegard D, Aspberg A
    The proteoglycans aggrecan and Versican form networks with fibulin-2 through their lectin domain binding. The Journal of biological chemistry 2001 Jan 12;276(2):1253-61
  7. Hsia HC, Schwarzbauer JE
    Meet the tenascins: multifunctional and mysterious. The Journal of biological chemistry 2005 Jul 22;280(29):26641-4
  8. Ochieng J, Leite-Browning ML, Warfield P
    Regulation of cellular adhesion to extracellular matrix proteins by galectin-3. Biochemical and biophysical research communications 1998 May 29;246(3):788-91
  9. Wu AM, Wu JH, Tsai MS, Liu JH, Andre S, Wasano K, Kaltner H, Gabius HJ
    Fine specificity of domain-I of recombinant tandem-repeat-type galectin-4 from rat gastrointestinal tract (G4-N). The Biochemical journal 2002 Nov 1;367(Pt 3):653-64
  10. Fischer C, Sanchez-Ruderisch H, Welzel M, Wiedenmann B, Sakai T, Andre S, Gabius HJ, Khachigian L, Detjen KM, Rosewicz S
    Galectin-1 Interacts with the {alpha}5{beta}1 Fibronectin Receptor to Restrict Carcinoma Cell Growth via Induction of p21 and p27. The Journal of biological chemistry 2005 Nov 4;280(44):37266-37277
  11. Blom AM, Thuveson M, Fries E
    Intracellular coupling of bikunin and the heavy chain of rat pre-alpha-inhibitor in COS-1 cells. The Biochemical journal 1997 Nov 15;328 ( Pt 1):185-91
  12. Cuvelier A, Muir JF, Martin JP, Sesboue R
    [Proteins of the inter-alpha trypsin inhibitor (ITI) family. A major role in the biology of the extracellular matrix] Revue des maladies respiratoires 2000 Apr;17(2):437-46
  13. Ledoux D, Papy-Garcia D, Escartin Q, Sagot MA, Cao Y, Barritault D, Courtois J, Hornebeck W, Caruelle JP
    Human plasmin enzymatic activity is inhibited by chemically modified dextrans. The Journal of biological chemistry 2000 Sep 22;275(38):29383-90
  14. Ala-aho R, Kahari VM
    Collagenases in cancer. Biochimie 2005 Mar-Apr;87(3-4):273-86
  15. Shvyrkova IG, Muranova TA
    [Proteolytic specificity of plasmin with respect to adhesive proteins] Bioorganicheskaia khimiia 2000 May;26(5):352-6
  16. Sounni NE, Noel A
    Membrane type-matrix metalloproteinases and tumor progression. Biochimie 2005 Mar-Apr;87(3-4):329-42