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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 exists between endocytosis and degradation, suggesting that endocytosis is more than a simple negative feedback. Phospholipase D (PLD), which has been implicated in vesicle formation in the Golgi, is activated in response to EGF and other growth factors. We report here that EGF receptor endocytosis is dependent upon PLD and the PLD1 regulators, protein kinase C alpha  and RalA. EGF-induced receptor degradation is accelerated by overexpression of either wild-type PLD1 or PLD2 and retarded by overexpression of catalytically inactive mutants of either PLD1 or PLD2. EGF-induced activation of mitogen-activated protein kinase, which is dependent upon receptor endocytosis, is also dependent upon PLD. These data suggest a role for PLD in signaling that facilitates receptor endocytosis.


* 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.


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.



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