title: Glycan-deficient PrP stimulates VEGFR2 signaling via glycosaminoglycan.
abstract: Whether the two N-linked glycans are important in prion, PrP, biology is unresolved. In Chinese hamster ovary (CHO) cells, the two glycans are clearly not important in the cell surface expression of transfected human PrP. Compared to fully-glycosylated PrP, glycan-deficient PrP preferentially partitions to lipid raft. In CHO cells glycan-deficient PrP also interacts with glycosaminoglycan (GAG) and vascular endothelial growth factor receptor 2 (VEGFR2), resulting in VEGFR2 activation and enhanced Akt phosphorylation. Accordingly, CHO cells expressing glycan-deficient PrP lacking the GAG binding motif or cells treated with heparinase to remove GAG show diminished Akt signaling. Being in lipid raft is critical, chimeric glycan-deficient PrP with CD4 transmembrane and cytoplasmic domains is absent in lipid raft and does not activate Akt signaling. CHO cells bearing glycan-deficient PrP also exhibit enhanced cellular adhesion and migration. Based on these findings, we propose a model in which glycan-deficient PrP, GAG, and VEGFR2 interact, activating VEGFR2 and resulting in changes in cellular behavior.
authors.affiliation: University of Chinese Academy of Sciences, Center for Molecular Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, 44 Xiao Hong Shan Zhong Qu, Wuhan 430071, China; Department of Virology, School of Life Sciences, Wuhan University, State Key Laboratory of Virology, Wuhan 430072, China.
authors.forename: Zhenxing
authors.initials: Z
authors.lastname: Gao
authors.affiliation: University of Chinese Academy of Sciences, Center for Molecular Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, 44 Xiao Hong Shan Zhong Qu, Wuhan 430071, China.
authors.forename: Huixia
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Wuhan Brain Hospital, No. 5 Huiji Road, Jiang'an District, Wuhan 430010, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Hu
authors.affiliation: University of Chinese Academy of Sciences, Center for Molecular Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, 44 Xiao Hong Shan Zhong Qu, Wuhan 430071, China; Department of Virology, School of Life Sciences, Wuhan University, State Key Laboratory of Virology, Wuhan 430072, China.
authors.forename: Liheng
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of the First Abdominal Surgery, Jiangxi Tumor Hospital, Nanchang 330029, China.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Virology, School of Life Sciences, Wuhan University, State Key Laboratory of Virology, Wuhan 430072, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Pathology, School of Medicine, Case Western Reserve University, 2106 Cornell Road, Cleveland, OH 44106, USA.
authors.forename: Man-Sun
authors.initials: MS
authors.lastname: Sy
authors.affiliation: Center for Molecular Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, State Key Laboratory of Virology, Wuhan Brain Hospital, 44 Xiao Hong Shan Zhong Qu, Wuhan 430071, China. Electronic address: cyli@wh.iov.cn.
authors.forename: Chaoyang
authors.initials: C
authors.lastname: Li
mesh_terms: D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion; D002465:Cell Movement; D006224:Cricetinae; D003412:Cricetulus; D006025:Glycosaminoglycans / Q000378:metabolism*; D006031:Glycosylation; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D006801:Humans; D021962:Membrane Microdomains / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011134:Polysaccharides / Q000378:metabolism; D018621:PrPC Proteins / Q000737:chemistry / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D006025:Glycosaminoglycans; D017261:Glycosylphosphatidylinositols; D011134:Polysaccharides; D018621:PrPC Proteins; D019869:Phosphatidylinositol 3-Kinases; D040301:Vascular Endothelial Growth Factor Receptor-2; D051057:Proto-Oncogene Proteins c-akt
keywords: GAG; Lipid raft; N-linked glycosylation; PrP; VEGFR2