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First published online 13 July 2004
doi: 10.1242/jcs.01220
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Research Article |
1 is a guanine nucleotide exchange factor for dynamin-1 and enhances dynamin-1-dependent epidermal growth factor receptor endocytosis
1 Division of Molecular and Life Science, Pohang University of Science and Technology, San 31, Hyojadong, Pohang, Kyungbuk 790-784, Republic of Korea
2 Department of Physiology, College of Medicine, Pusan National University, Pusan, 602-739, Republic of Korea
3 Green Cross Institute of Medical Genetics, 164-10 Po Yi-Dong, Seoul, 135-260, Republic of Korea
4 Departments of Neuroscience, Pharmacology and Molecular Sciences and Psychiatry, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205 USA
* Author for correspondence (e-mail: pgs{at}postech.ac.kr)
Accepted 12 March 2004
Phospholipase C-
1 (PLC-1), which interacts with a variety of signaling molecules through its two Src homology (SH) 2 domains and a single SH3 domain has been implicated in the regulation of many cellular functions. We demonstrate that PLC-1 acts as a guanine nucleotide exchange factor (GEF) of dynamin-1, a 100 kDa GTPase protein, which is involved in clathrin-mediated endocytosis of epidermal growth factor (EGF) receptor. Overexpression of PLC-1 increases endocytosis of the EGF receptor by increasing guanine nucleotide exchange activity of dynamin-1. The GEF activity of PLC-1 is mediated by the direct interaction of its SH3 domain with dynamin-1. EGF-dependent activation of ERK and serum response element (SRE) are both up-regulated in PC12 cells stably overexpressing PLC-1, but knockdown of PLC-1 by siRNA significantly reduces ERK activation. These results establish a new role for PLC-1 in the regulation of endocytosis and suggest that endocytosis of activated EGF receptors may mediate PLC-1-dependent proliferation.
Key words: Phospholipase C-1, Dynamin-1, Guanine nucleotide exchange factor (GEF), Endocytosis, Proliferation
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