Phospholipase C-γ1 is a guanine nucleotide exchange factor for dynamin-1 and enhances dynamin-1-dependent epidermal growth factor receptor endocytosis

Jang Hyun Choi, Jong Bae Park, Sun Sik Bae, Sanguk Yun, Hyeon Soo Kim, Won Pyo Hong, Il Shin Kim, Jae Ho Kim, Mi Young Han, Sung Ho Ryu, Randen L. Patterson, Solomon H. Synder, Pan Ghill Suh

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41 Citations (Scopus)

Abstract

Phospholipase C-γ1 (PLC-γ1), 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-γ1 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-γ1 increases endocytosis of the EGF receptor by increasing guanine nucleotide exchange activity of dynamin-1. The GEF activity of PLC-γ1 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-γ1, but knockdown of PLC-γ1 by ARNA significantly reduces ERK activation. These results establish a new role for PLC-γ1 in the regulation of endocytosis and suggest that endocytosis of activated EGF receptors may mediate PLC-γ 1-dependent proliferation.

Original languageEnglish
Pages (from-to)3785-3795
Number of pages11
JournalJournal of Cell Science
Volume117
Issue number17
DOIs
Publication statusPublished - 2004 Aug 1
Externally publishedYes

Keywords

  • Dynamin-1
  • Endocytosis
  • Guanine nucleotide exchange factor (GEF)
  • Phospholipase C-γ1
  • Proliferation

ASJC Scopus subject areas

  • Cell Biology

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  • Cite this

    Choi, J. H., Park, J. B., Bae, S. S., Yun, S., Kim, H. S., Hong, W. P., Kim, I. S., Kim, J. H., Han, M. Y., Ryu, S. H., Patterson, R. L., Synder, S. H., & Suh, P. G. (2004). Phospholipase C-γ1 is a guanine nucleotide exchange factor for dynamin-1 and enhances dynamin-1-dependent epidermal growth factor receptor endocytosis. Journal of Cell Science, 117(17), 3785-3795. https://doi.org/10.1242/jcs.01220