title: Association of protein-tyrosine phosphatase MEG2 via its Sec14p homology domain with vesicle-trafficking proteins.
abstract: The protein-tyrosine phosphatase PTPMEG2 is located on the cytoplasmic face of the enclosing membrane of secretory vesicles, where it regulates vesicle size by promoting homotypic vesicle fusion by dephosphorylating N-ethylmaleimide-sensitive factor, a key regulator of vesicle fusion. Here we address the question of how PTPMEG2 is targeted to this subcellular location. Using a series of deletion mutants, we pinpointed the N-terminal Sec14p homology (SEC14) domain of PTPMEG2, residues 1-261, as the region containing the secretory vesicle targeting signal. This domain, alone or appended to a heterologous protein, was localized to intracellular vesicle membranes. Yeast two-hybrid screening identified a number of secretory vesicle proteins that interacted directly with the SEC14 domain of PTPMEG2, providing a mechanism for PTPMEG2 targeting to secretory vesicles. Two such proteins, mannose 6-phosphate receptor-interacting protein TIP47 and Arfaptin2, were found to alter PTPMEG2 localization when overexpressed, and elimination of TIP47 resulted in loss of PTPMEG2 function. We conclude that the N terminus of PTPMEG2 is necessary for the targeting of this phosphatase to the secretory vesicle compartment by association with other proteins involved in intracellular transport.
authors: Program on Inflammatory Disease Research, Infectious and Inflammatory Disease Center, and Program of Signal Transduction, Cancer Center, The Burnham Institute for Medical Research, La Jolla, California 92037, USA.
authors: Kan
authors: K
authors: Saito
authors: Scott
authors: S
authors: Williams
authors: Anna
authors: A
authors: Bulankina
authors: Stefan
authors: S
authors: Höning
authors: Tomas
authors: T
authors: Mustelin
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D001693:Biological Transport, Active / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D000070796:Perilipin-3; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000235:genetics; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D050683:R-SNARE Proteins / Q000235:genetics / Q000378:metabolism*; D022142:Secretory Vesicles / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D033921:Vesicular Transport Proteins
chemical_list: C101158:ARFIP2 protein, human; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C038196:PLIN3 protein, human; D000070796:Perilipin-3; D011257:Pregnancy Proteins; D050683:R-SNARE Proteins; D033921:Vesicular Transport Proteins; C447615:PTPN9 protein, human; D017027:Protein Tyrosine Phosphatases; D054558:Protein Tyrosine Phosphatases, Non-Receptor