Institute of Biological Chemistry, Academia Sinica
gcchen@gate.sinica.edu.tw
+886-2-2785-5696,7010,7011
Functional analysis of PTPs in development and human diseases
Protein tyrosine phosphatases (PTPs) are a group of tightly regulated enzymes that coordinate with protein tyrosine kinases (PTKs) to control protein phosphorylation during cell adhesion and migration. To explore the functional role of PTPs in cell adhesion and migration, we performed genetic analyses to identify PTPs that could modulate border cell migration during Drosophila oogenesis. Depletion of Myopic (Mop), the Drosophila homolog of human HDPTP/PTPN23, resulted in aberrant integrin distribution and border cell dissociation. We further identified Rab4 GTPase as an interactor of Mop/HDPTP. HDPTP regulates Rab4 distribution, integrin trafficking, and cell motility. We also found that the FERM and PDZ domain-containing protein tyrosine phosphatase, dPtpmeg/PTPN3, negatively regulates EGFR/Ras/MAPK signaling pathway. Our recent data indicate that PTPN3 promotes EGFR degradation and inhibits lung cancer cell proliferation and migration.
Molecular signaling and PTM of autophagy
Autophagy is a process by which components of the cytoplasm (the jelly-like substance that fills a cell) are engulfed and degraded; it has recently been found to play an important role in development and in certain human diseases such as cancer, immune response, and neurodegeneration. We are applying genetic, cell biologic, and biochemical approaches to study the molecular machinery of autophagy.
K48/K63-linked polyubiquitination of ATG9A by TRAF6 E3 ligase regulates oxidative stress-induced autophagy.
Wang YT, Liu TY, Shen CH, Lin SY, Hung CC, Hsu LC, Chen GC
Cell Reports (2022)
PTPN9-mediated dephosphorylation of VTI1B promotes ATG16L1 precursor fusion and autophagosome formation.
Chou HY, Lee YT, Lin YJ, Wen JK, Peng WH, Hsieh PL, Lin SY, Hung CC, Chen GC
Autophagy (2021)
PTPN3 suppresses lung cancer cell invasiveness by counteracting Src-mediated DAAM1 activation and actin polymerization.
Li MY, Peng WH, Wu CH, Chang YM, Lin YL, Chang GD, Wu HC, Chen GC
Oncogene (2019)
Atg9 antagonizes TOR signaling to regulate intestinal cell growth and epithelial homeostasis in Drosophila.
Wen JK, Wang YT, Chan CC, Hsieh CW, Liao HM, Hung CC, and Chen GC
eLife (2017)
The role of ubiquitin system in autophagy.
Wang YT and Chen GC
Autophagy in Current Trends in Cellular Physiology and Pathology (2016)
Protein tyrosine phosphatase PTPN3 inhibits lung cancer cell proliferation and migration by promoting EGFR endocytic degradation.
Li MY, Lai PL, Chou YT, Chi AP, Mi YZ, Khoo KH, Chang GD, Wu CW, Meng TC, Chen GC
Oncogene (2015)
Ecdysone-induced receptor tyrosine phosphatase PTP52F regulates Drosophila midgut histolysis by enhancement of autophagy and apoptosis.
Santhanam A, Peng WH, Yu YT, Sang TK, Chen GC, Meng TC
Mol Cell Biol. (2014)
Atg9 Interacts with dTRAF2/TRAF6 to Regulate Oxidative Stress-Induced JNK Activation and Autophagy Induction.
Hong-Wen Tang, Hsiao-Man Liao, Wen-Hsin Peng, Hong-Ru Lin, Chun-Hong Chen, Guang-Chao Chen
Developmental Cell (2013)
The Bro1-domain-containing protein Myopic/HDPTP coordinates with Rab4 to regulate cell adhesion and migration.
Chen DY, Li MY, Wu SY, Lin YL, Tsai SP, Lai PL, Lin YT, Kuo JC, Meng TC, Chen GC
J Cell Sci. (2012)
Atg1-mediated myosin II activation regulates autophagosome formation during starvation-induced autophagy.
Tang HW, Wang YB, Wang SL, Wu MH, Lin SY, Chen GC
EMBO JOURNAL (2011)
