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J Biol Chem, Vol. 273, Issue 6, 3121-3124, February 6, 1998

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

Sandip Patel, Manoranjan Santra, David J. McQuillan^¶, Renato V. Iozzo, and Andrew P. Thomas

From the  Department of Pathology, Anatomy and Cell Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, the ^¶ Center for Extracellular Matrix Biology, Institute of Biosciences and Technology, Texas A & M University, Houston, Texas 77030, and the  Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107

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 Ca²⁺ levels of single A431 cells. The effects of decorin persisted in the absence of extracellular Ca²⁺ 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 Ca²⁺ providing a possible mechanism by which decorin causes growth suppression.

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Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.

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