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Enhanced expression and phosphorylation of the MET oncoprotein by glioma‐specific PTPRZ1–MET fusions
Author(s) -
Chen Hui-Min,
Yu Kai,
Tang Xiao-yan,
Bao Zhao-shi,
Jiang Tao,
Fan Xiao-Long,
Chen Xiao-Wei,
Su Xiao-Dong
Publication year - 2015
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2015.04.032
Subject(s) - phosphorylation , hepatocyte growth factor , glioma , protein tyrosine phosphatase , phosphatase , hepatocyte growth factor receptor , biology , cancer research , fusion protein , tyrosine phosphorylation , receptor tyrosine kinase , fusion gene , growth factor , microbiology and biotechnology , receptor , gene , c met , recombinant dna , genetics
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.