title: Cdc42 induces EGF receptor protein accumulation and promotes EGF receptor nuclear transport and cellular transformation.
abstract: Cdc42 is a Ras-related small GTP-binding protein. A previous study has shown that Cdc42 binding to the γ subunit of the coatomer protein complex (γCOP) is essential for Cdc42-regulated cellular transformation, but the molecular mechanism involved is not well understood. Here, we demonstrate that constitutively-active Cdc42 binding to γCOP induced the accumulation of epithelial growth factor receptor (EGFR) in the cells, sustained EGF-stimulated extracellular signal-regulated kinase (ERK), JUN amino-terminal kinase (JNK) and phosphoinositide 3-kinase (PI3K) signaling and promoted cell division. Moreover, constitutive Cdc42 activity facilitated the nuclear translocation of EGFR, and this indicates a novel mechanism through which Cdc42 might promote cellular transformation.
authors.affiliation: Institute of Translational Medicine, Nanchang University, Jiangxi 330031, China.
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Wang
authors.affiliation: Institute of Translational Medicine, Nanchang University, Jiangxi 330031, China.
authors.forename: Ming-Xi
authors.initials: MX
authors.lastname: Gan
authors.affiliation: Institute of Translational Medicine, Nanchang University, Jiangxi 330031, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Translational Medicine, Nanchang University, Jiangxi 330031, China.
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Zhan
authors.affiliation: Institute of Translational Medicine, Nanchang University, Jiangxi 330031, China.
authors.forename: Tian-Yu
authors.initials: TY
authors.lastname: Han
authors.affiliation: Institute of Translational Medicine, Nanchang University, Jiangxi 330031, China.
authors.forename: Xiao-Jian
authors.initials: XJ
authors.lastname: Han
authors.affiliation: Department of Molecular Oncology, H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA.
authors.forename: Jin-Quan
authors.initials: JQ
authors.lastname: Cheng
authors.affiliation: Institute of Translational Medicine, Nanchang University, Jiangxi 330031, China. Electronic address: jianbinwang1@gmail.com.
authors.forename: Jian-Bin
authors.initials: JB
authors.lastname: Wang
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D051379:Mice; D009154:Mutation; D041681:NIH 3T3 Cells; D011485:Protein Binding; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D066246:ErbB Receptors; D020764:cdc42 GTP-Binding Protein
keywords: Cell transformation; EGF receptor; MAP kinases; Small GTP-binding protein; γCOP of coatomer protein complex