Enhanced expression and phosphorylation of the MET oncoprotein by glioma-specific PTPRZ1-MET fusions

Hui-Min Chen; Kai Yu; Xiao-yan Tang; Zhao-shi Bao; Tao Jiang; Xiao-Long Fan; Xiao-Wei Chen; Xiao-Dong Su

doi:10.1016/j.febslet.2015.04.032

Enhanced expression and phosphorylation of the MET oncoprotein by glioma-specific PTPRZ1-MET fusions

FEBS Lett. 2015 Jun 4;589(13):1437-43. doi: 10.1016/j.febslet.2015.04.032. Epub 2015 Apr 29.

Authors

Hui-Min Chen¹, Kai Yu², Xiao-yan Tang², Zhao-shi Bao³, Tao Jiang³, Xiao-Long Fan⁴, Xiao-Wei Chen⁵, Xiao-Dong Su⁶

Affiliations

¹ 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.
² Biodynamic Optical Imaging Center (BIOPIC), School of Life Sciences, Peking University, Beijing 100871, China.
³ Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China; Beijing Neurosurgical Institute, Beijing 100050, China.
⁴ Laboratory of Neuroscience and Brain Development, Beijing Key Laboratory of Gene Resource and Molecular Development, Beijing Normal University, Beijing, China.
⁵ Institute of Molecular Medicine, Centre for Life Sciences, Peking University, Beijing 100871, China.
⁶ Biodynamic Optical Imaging Center (BIOPIC), School of Life Sciences, Peking University, Beijing 100871, China. Electronic address: xdsu@pku.edu.cn.

PMID: 25935522
DOI: 10.1016/j.febslet.2015.04.032

Abstract

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.

Keywords: Dimerization; Expression level; Fusion gene; Hepatocyte growth factor receptor; Phosphorylation; Receptor-type tyrosine-protein phosphatase zeta.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Blotting, Western
Gene Expression Regulation, Neoplastic*
HEK293 Cells
Hepatocyte Growth Factor / pharmacology
Humans
Oncogene Proteins, Fusion / chemistry
Oncogene Proteins, Fusion / genetics*
Oncogene Proteins, Fusion / metabolism
Phosphorylation / drug effects
Protein Multimerization
Proto-Oncogene Proteins c-met / chemistry
Proto-Oncogene Proteins c-met / genetics*
Proto-Oncogene Proteins c-met / metabolism
RNA, Messenger / genetics
RNA, Messenger / metabolism
Receptor-Like Protein Tyrosine Phosphatases, Class 5 / chemistry
Receptor-Like Protein Tyrosine Phosphatases, Class 5 / genetics*
Receptor-Like Protein Tyrosine Phosphatases, Class 5 / metabolism
Reverse Transcriptase Polymerase Chain Reaction

Substances

Oncogene Proteins, Fusion
RNA, Messenger
Hepatocyte Growth Factor
MET protein, human
Proto-Oncogene Proteins c-met
PTPRZ1 protein, human
Receptor-Like Protein Tyrosine Phosphatases, Class 5