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.