Role for Phospholipase D in Receptor-Mediated Endocytosis

doi:10.1128/MCB.21.2.595-602.2001

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Molecular and Cellular Biology, January 2001, p. 595-602, Vol. 21, No. 2
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.2.595-602.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Role for Phospholipase D in Receptor-Mediated Endocytosis

Yingjie Shen, Lizhong Xu, and David A. Foster^*

Department of Biological Sciences, Hunter College of The City University of New York, New York, New York 10021

Received 22 June 2000/Returned for modification 27 July 2000/Accepted 12 October 2000

In response to epidermal growth factor (EGF), the EGF receptor is endocytosed and degraded. A substantial lag period existsbetween endocytosis and degradation, suggesting that endocytosisis more than a simple negative feedback. Phospholipase D (PLD),which has been implicated in vesicle formation in the Golgi, isactivated in response to EGF and other growth factors. We reporthere that EGF receptor endocytosis is dependent upon PLD and thePLD1 regulators, protein kinase C $alpha$ and RalA. EGF-induced receptordegradation is accelerated by overexpression of either wild-typePLD1 or PLD2 and retarded by overexpression of catalytically inactivemutants of either PLD1 or PLD2. EGF-induced activation of mitogen-activatedprotein kinase, which is dependent upon receptor endocytosis,is also dependent upon PLD. These data suggest a role for PLDin signaling that facilitates receptorendocytosis.

^* Corresponding author. Mailing address: Department of Biological Sciences, Hunter College of The City University of New York,695 Park Ave., New York, NY 10021. Phone: (212) 772-4075. Fax:(212) 772-5227. E-mail: foster{at}genectr.hunter.cuny.edu.

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