The pleckstrin homology domain of phospholipase D1 accelerates EGFR endocytosis by increasing the expression of the Rab5 effector, rabaptin-5.
- Author:
Mi Hee PARK
1
;
Kang Yell CHOI
;
Do Sik MIN
Author Information
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- MeSH: Animals; Blood Proteins/chemistry/*metabolism; Endocytosis; Female; HEK293 Cells; HT29 Cells; Humans; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism; Mice, Nude; Neoplasms/genetics/metabolism/pathology; Phospholipase D/chemistry/*metabolism; Phosphoproteins/chemistry/*metabolism; Protein Structure, Tertiary; Receptor, Epidermal Growth Factor/*metabolism; Signal Transduction; *Up-Regulation; Vesicular Transport Proteins/*genetics/metabolism; rab5 GTP-Binding Proteins/*metabolism
- From:Experimental & Molecular Medicine 2015;47(12):e200-
- CountryRepublic of Korea
- Language:English
- Abstract: Endocytosis is differentially regulated by hypoxia-inducible factor-1alpha (HIF-1alpha) and phospholipase D (PLD). However, the relationship between HIF-1alpha and PLD in endocytosis is unknown. HIF-1alpha is degraded through the prolyl hydroxylase (PHD)/von Hippel-Lindau (VHL) ubiquitination pathway in an oxygen-dependent manner. Here, we show that PLD1 recovers the decrease in epidermal growth factor receptor (EGFR) endocytosis induced by HIF-1alpha independent of lipase activity via the Rab5-mediated endosome fusion pathway. EGF-induced interaction of PLD1 with HIF-1alpha, PHD and VHL may contribute to EGFR endocytosis. The pleckstrin homology domain (PH) of PLD1 itself promotes degradation of HIF-1alpha, then accelerates EGFR endocytosis via upregulation of rabaptin-5 and suppresses tumor progression. These findings reveal a novel role of the PLD1-PH domain as a positive regulator of endocytosis and provide a link between PLD1 and HIF-1alpha in the EGFR endocytosis pathway.
