Specific Interaction of Protein Tyrosine Phosphatase-MEG2 with Phosphatidylserine

Abstract

Protein tyrosine phosphatase (PTP)-MEG2 is an intracellular tyrosine phosphatase that contains a Sec14 homology domain. We have purified the full-length and truncated forms of the enzyme from recombinant adenovirus-infected human 293 cells. By using lipid-membrane overlay and liposome binding assays, we demonstrated that PTP-MEG2 specifically binds phosphatidylserine among over 20 lipid compounds tested. The binding is mediated by its N-terminal Sec14 domain. In intact cells, the Sec14 domain is responsible for localization of PTP-MEG2 to the perinuclear region, and uploading of PS into the cell membrane causes translocation of PTP-MEG2 to the plasma membrane. Phosphatidylserine is a relatively abundant cell membrane phospholipid non-symmetrically distributed in the outer layer and inner layer of cell membranes. It has recently been defined as an important ligand for clearance of apoptotic cells. By specifically binding phosphatidylserine, PTP-MEG2 may play an important role in regulating signaling processes associated with phagocytosis of apoptotic cells.