+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Meltrin gamma(ADAM-9) mediates cellular adhesion through alpha(6)beta(1 )integrin, leading to a marked induction of fibroblast cell motility



Meltrin gamma(ADAM-9) mediates cellular adhesion through alpha(6)beta(1 )integrin, leading to a marked induction of fibroblast cell motility



Journal of Cell Science 113: 2319-2328



The ADAMs (A Disintegrin and Metalloprotease Domains) are a family of membrane-anchored proteins that play a role in fertilisation, myoblast fusion and ectodomain shedding of cell surface proteins. Meltrin gamma (ADAM-9) is a widely expressed member of this family and is involved in the shedding of heparin binding epidermal growth factor. Here we report that meltrin gamma can function as a cell adhesion molecule via its disintegrin domain. Using solid-phase binding assays and antibody inhibition experiments, we demonstrate that a murine meltrin gamma-Fc (Mel gamma -Fc) fusion protein binds to the integrin alpha(6)beta(1) on the surface of fibroblast cell lines, HT1080 and Wehi 164 in a specific manner. Since alpha(6)beta(1) is important for the motility of several cell types on laminin, cell migration studies using time-lapse video microscopy were performed. Cells adhering to Mel gamma-Fc displayed a rounded morphology and a marked increase (eight- to tenfold) in their motility compared to that on laminin. Furthermore, the p160 ROCK kinase inhibitor Y-27632 specifically reduced the migration of cells on meltrin gamma but had no effect on migration of cells on laminin, whilst the general tyrosine phoshorylation inhibitor, genistein, inhibited cell migration on both substrates. These results together suggest that meltrin gamma may play a role in regulating the motility of cells by binding to alpha(6)beta(1) integrin and this may be important during a variety of biological and pathological processes.

(PDF emailed within 1 workday: $29.90)

Accession: 046661053

Download citation: RISBibTeXText

PMID: 10825303


Related references

Meltrin c(ADAM-9) mediates cellular adhesion through a6b1 integrin, leading to a marked induction of fibroblast cell motility. Journal of Cell Science 113(12): 8, 2000

MDC-9 (ADAM-9/Meltrin gamma) functions as an adhesion molecule by binding the alpha(v)beta(5) integrin. Biochemical and Biophysical Research Communications 280(2): 574-580, 2001

ADAM-9 (MDC-9/meltrin-gamma), a member of the a disintegrin and metalloproteinase family, regulates myeloma-cell-induced interleukin-6 production in osteoblasts by direct interaction with the alpha(v)beta5 integrin. Blood 107(8): 3271-3278, 2005

Integrin alpha v beta 3 mediates K1735 murine melanoma cell motility via activation of focal adhesion kinase and C-Src. Proceedings of the American Association for Cancer Research Annual Meeting 42: 839, 2001

Cysteine-rich domain of human ADAM 12 (meltrin alpha) supports tumor cell adhesion. American Journal of Pathology 154(5): 1489-1501, 1999

Alpha 4 beta 7 integrin mediates B cell binding to fibronectin and vascular cell adhesion molecule-1. Expression and function of alpha 4 integrins on human B lymphocytes. Journal of Immunology 151(5): 2471-2483, 1993

Myeloperoxidase mediates cell adhesion via the alpha M beta 2 integrin (Mac-1, CD11b/CD18). Journal of Cell Science 110: 1133-1139, 1997

Human recombinant osteopontin selectively mediates cell adhesion via the alpha-V-beta-3 integrin. Molecular Biology of the Cell 6(SUPPL ): 45A, 1995

Inside-out intergrin signaling in macrophages: Analysis of the role of the alpha-6A-beta-1 and alpha-6B-beta-1 integrin variants in laminin adhesion by cDNA expression in an alpha-6 integrin-deficient macrophage cell line. Journal of Biological Chemistry 268(15): 11401-11408, 1993

The activation state of the integrin alpha IIb beta 3 affects outside-in signals leading to cell spreading and focal adhesion kinase phosphorylation. Journal of Biological Chemistry 270(30): 18133-18140, 1995

Alpha-7 Integrin mediates myoblast adhesion and motility on specific laminin isoforms. Molecular Biology of the Cell 7(SUPPL ): 587A, 1996

Alpha 4/beta 1 integrin (VLA-4) ligands in arthritis. Vascular cell adhesion molecule-1 expression in synovium and on fibroblast-like synoviocytes. Journal of Immunology 149(4): 1424-1431, 1992

Receptor tyrosine kinase signaling required for integrin alpha v beta 5-directed cell motility but not adhesion on vitronectin. Journal of Cell Biology 127(3): 859-866, 1994

Integrin alpha E(CD103)beta 7 mediates adhesion to intestinal microvascular endothelial cell lines via an E-cadherin-independent interaction. Journal of Immunology 166(5): 3506-3514, 2001

Cbl associates with Pyk2 and Src to regulate Src kinase activity, alpha(v)beta(3) integrin-mediated signaling, cell adhesion, and osteoclast motility. Journal of Cell Biology 152(1): 181-195, 2001