Mitogen-activated protein kinase-dependent and -independent routes control shedding of transmembrane growth factors through multiple secretases

The Biochemical Journal
J C MonteroA Pandiella

Abstract

Solubilization of a number of membrane proteins occurs by the action of cell-surface proteases, termed secretases. Recently, the activity of these secretases has been reported to be controlled by the extracellular signal-regulated kinases 1 and 2 (ERK1/ERK2) and the p38 mitogen-activated protein kinase (MAPK) routes. In the present paper, we show that shedding of membrane-anchored growth factors (MAGFs) may also occur through MAPK-independent routes. In Chinese-hamster ovary cells, cleavage induced by protein kinase C (PKC) stimulation was largely insensitive to inhibitors of the ERK1/ERK2 and p38 routes. Other reagents such as sorbitol or UV light stimulated MAGF cleavage independent of PKC. The action of sorbitol on cleavage was only partially prevented by the combined action of inhibitors of the p38 and ERK1/ERK2 routes, indicating that sorbitol can also stimulate shedding by MAPK-dependent and -independent routes. Studies in cells devoid of activity of the secretase tumour necrosis factor-alpha-converting enzyme (TACE) indicated that this protease had an essential role in PKC- and ERK1/ERK2-mediated shedding. However, secretases other than TACE may also cleave MAGFs since sorbitol could still induce shedding in these cells....Continue Reading

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Citations

Apr 17, 2008·Journal of Mammary Gland Biology and Neoplasia·Nandini V L Hayes, William J Gullick
Mar 31, 2012·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Peter D PioliJohn J Krolewski
Mar 11, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·April KalinowskiKerry S Russell
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Jun 23, 2004·European Journal of Biochemistry·Monika BzowskaJoanna Bereta
May 12, 2009·American Journal of Physiology. Lung Cellular and Molecular Physiology·Suil Kim, Jay A Nadel
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Mar 3, 2011·Cellular and Molecular Life Sciences : CMLS·Maria Dolores Gutiérrez-LópezCarlos Cabañas
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Jul 18, 2006·Gynecologic Oncology·Kenzo SonodaHitoo Nakano
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Aug 18, 2020·Cellular and Molecular Life Sciences : CMLS·Juan Carlos Montero, Atanasio Pandiella
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Jun 4, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Juan Carlos MonteroAtanasio Pandiella
Aug 23, 2005·Gynecologic Oncology·Kenzo SonodaHitoo Nakano

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