Decorin Activates the Epidermal Growth Factor Receptor and Elevates Cytosolic Ca2+ in A431 Carcinoma Cells

• Published in: The Journal of biological chemistry Vol. 273; no. 6; pp. 3121 - 3124
• Main Authors: Patel, S, Santra, M, McQuillan, D J, Iozzo, R V, Thomas, A P
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 06.02.1998
• Subjects: Calcium - metabolism; Cell Division - physiology; Cytosol - metabolism; Decorin; Down-Regulation; Enzyme Inhibitors - pharmacology; ErbB Receptors - antagonists & inhibitors; ErbB Receptors - metabolism; Extracellular Matrix Proteins; Humans; Nitriles - pharmacology; Proteoglycans - physiology; Quinazolines - pharmacology; Signal Transduction; Tumor Cells, Cultured; Tyrphostins
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.273.6.3121

Several independent lines of evidence have implicated decorin, a small leucine-rich proteoglycan, in the inhibition of cell proliferation. However, the mechanism by which decorin mediates its effect on cell proliferation is unclear. Here we report, for the first time, decorin-mediated increases in intracellular Ca 2+ levels of single A431 cells. The effects of decorin persisted in the absence of extracellular Ca 2+ but were blocked by AG1478, an epidermal growth factor (EGF)-specific tyrosine kinase inhibitor, and by down-regulation of the EGF receptor. The effects of decorin were not mimicked by the structurally homologous protein, biglycan. Our results indicate a novel action of decorin on the EGF receptor, which results in mobilization of intracellular Ca 2+ providing a possible mechanism by which decorin causes growth suppression.