Title

The epidermal growth factor receptor (EGFR) is proteolytically modified by the Matriptase-Prostasin serine protease cascade in cultured epithelial cells

Authors

Authors

M. Chen; L. M. Chen; C. Y. Lin;K. X. Chai

Comments

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Abbreviated Journal Title

Biochim. Biophys. Acta-Mol. Cell Res.

Keywords

ErbB receptor tyrosine kinase; GPI-anchor; transmembrane glycoprotein; extracellular signal-regulated kinase; MT-SP1; PRSS8; TYROSINE KINASE; MESSENGER-RNA; BREAST-CANCER; GENE-EXPRESSION; DOWN-REGULATION; SODIUM-CHANNEL; ACTIVATION; PATHWAY; ERBB2; LINES; Biochemistry & Molecular Biology; Cell Biology

Abstract

Prostasin is expressed at the apical surface of normal epithelial cells and suppresses in vitro invasion of cancer cells. Prostasin re-expression in the PC-3 prostate carcinoma cells down-regulated the epidermal growth factor receptor (EGFR) protein expression and EGF-induced phosphorylation of the extracellular signal-regulated kinases (Erk1/2). We report here that prostasin and its activating enzyme matriptase are capable of inducing proteolytic cleavages in the EGFR extracellular domain (ECD) when co-expressed in the FT-293 cells, generating two aminoterminally truncated fragments EGFR135 and EGFR110, at 135 and 110 kDa. Prostasin's role in EGFR cleavage is dependent on the serine active-site but not the GPI-anchor. The modifications of EGFR were confirmed to be on the primary structure by deglycosylation. EGFR135 and EGFR110 are notresponsive to EGF stimulation, indicating loss of the ligand-binding domains. EGFR110 is constitutively phosphorylated and in its presence Erk1/2 phosphorylation is increased in the absence of EGF. The protease-induced EGFR cleavages are not dependent on EGFR phosphorylation. The EGFR ECD proteolytic modification by matriptase-prostasin is also observed in the BEAS-2B normal lung epithelial cells, the BPH-1 benign prostate hyperplasia and the MDA-MB-231 breast cancer cell lines; and represents a novel mechanism for epithelial cells to modulate EGF-EGFR signaling. (C) 2007 Elsevier B.V All rights

Journal Title

Biochimica Et Biophysica Acta-Molecular Cell Research

Volume

1783

Issue/Number

5

Publication Date

1-1-2008

Document Type

Article

Language

English

First Page

896

Last Page

903

WOS Identifier

WOS:000255794200020

ISSN

0167-4889

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