PMID: 9548562Apr 21, 1998Paper

Extracellular calcium influx stimulates metalloproteinase cleavage and secretion of heparin-binding EGF-like growth factor independently of protein kinase C

Journal of Cellular Biochemistry
S M DethlefsenM R Freeman

Abstract

The phorbol ester, tetradecanoyl-phorbol 13-acetate (TPA), stimulates rapid proteolytic processing of the transmembrane, pro- form of heparin-binding epidermal growth factor-like growth factor (HB-EGF) at cell surfaces, suggesting the involvement of protein kinase C (PKC) isoforms in the HB-EGF secretion mechanism. To test this possibility, we expressed a chimeric protein, consisting of proHB-EGF fused to placental alkaline phosphatase (AP) near the amino terminus of processed HB-EGF, in NbMC-2 prostate epithelial cells. The proHB-EGF-AP chimera localized to plasma membranes and functioned as a diphtheria toxin receptor. Secreted HB-EGF-AP bound to heparin and exhibited potent growth factor activity. The presence of the AP moiety allowed highly quantitative measurements of cleavage-secretion responses of proHB-EGF to extracellular stimuli. As expected, rapid secretion of HB-EGF-AP was induced in a time- and dose-dependent manner by TPA. However, this was also observed with the Ca2+ ionophore, ionomycin, suggesting the involvement of extracellular Ca2+ ions in the secretion mechanism. Ionomycin-induced secretion was inhibited by extracellular calcium chelation but not by the PKC inhibitors, GF109203X, staurosporine, or cheleryth...Continue Reading

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Citations

Jan 30, 2004·Cytokine & Growth Factor Reviews·Daisuke Nanba, Shigeki Higashiyama
Oct 30, 2012·The Journal of Biological Chemistry·Annelize Z B AragãoAdriana F Paes Leme
Oct 3, 2002·The EMBO Journal·Claus-Werner FranzkeLeena Bruckner-Tuderman
Apr 20, 2013·Journal of Biochemistry·Hirofumi InoueShigeki Higashiyama
Mar 11, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·April KalinowskiKerry S Russell
Sep 16, 2003·American Journal of Respiratory Cell and Molecular Biology·Weidong WuLee M Graves
Nov 25, 2004·The Journal of Clinical Endocrinology and Metabolism·Katya ChobotovaHelen J Mardon
Feb 8, 2007·Journal of Cell Science·Jia YinFu-Shin X Yu
Mar 25, 2006·Cell Structure and Function·Xiaobiao WangEisuke Mekada
Feb 27, 2008·The Journal of Cell Biology·Miki HiedaShigeki Higashiyama
May 13, 2005·The British Journal of Dermatology·M KawaguchiS Kondo
Feb 15, 2008·Cancer Science·Shigeki HigashiyamaNatsuki Matsushita
Dec 3, 2008·International Journal of Cancer. Journal International Du Cancer·Hiroshi YagiShingo Miyamoto
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May 27, 2010·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Kazutaka HayashidaPyong Woo Park
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