Enhanced expression and phosphorylation of the MET oncoprotein by glioma-specific PTPRZ1-MET fusions.
PTPRZ1-MET (ZM) proteins are a group of fusion proteins identified in human gliomas by high-throughput transcriptome sequencing. ZM fusions are associated with poor prognosis in afflicted glioma patients and mediate oncogenic effects in assays. In this study, we show that ZM-carrying patients have increased hepatocyte growth factor receptor (MET) mRNA expression levels induced by fusion with receptor-type tyrosine-protein phosphatase zeta (PTPRZ1). Furthermore, ZM fusions preserve fundamental properties of wild-type MET with respect to processing and dimerization, and enhance phosphorylation in an hepatocyte growth factor (HGF)-dependent and independent manner. Our findings suggest that ZM induces gliomas through elevated expression and phosphorylation of the MET oncoprotein.
Biodynamic Optical Imaging Center (BIOPIC), School of Life Sciences, Peking University, Beijing 100871, China; School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, China.
Hui-Min
HM
Chen
Biodynamic Optical Imaging Center (BIOPIC), School of Life Sciences, Peking University, Beijing 100871, China.
Kai
K
Yu
Biodynamic Optical Imaging Center (BIOPIC), School of Life Sciences, Peking University, Beijing 100871, China.
Xiao-yan
XY
Tang
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China; Beijing Neurosurgical Institute, Beijing 100050, China.
Zhao-shi
ZS
Bao
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China; Beijing Neurosurgical Institute, Beijing 100050, China.
Tao
T
Jiang
Laboratory of Neuroscience and Brain Development, Beijing Key Laboratory of Gene Resource and Molecular Development, Beijing Normal University, Beijing, China.
Xiao-Long
XL
Fan
Institute of Molecular Medicine, Centre for Life Sciences, Peking University, Beijing 100871, China.
Xiao-Wei
XW
Chen
Biodynamic Optical Imaging Center (BIOPIC), School of Life Sciences, Peking University, Beijing 100871, China. Electronic address: xdsu@pku.edu.cn.
Xiao-Dong
XD
Su
D015153:Blotting, Western; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D006801:Humans; D015514:Oncogene Proteins, Fusion / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D055503:Protein Multimerization; D019859:Proto-Oncogene Proteins c-met / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; D017228:Hepatocyte Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; C516895:PTPRZ1 protein, human; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5
Dimerization; Expression level; Fusion gene; Hepatocyte growth factor receptor; Phosphorylation; Receptor-type tyrosine-protein phosphatase zeta