Enlargement of secretory vesicles by protein tyrosine phosphatase PTP-MEG2 in rat basophilic leukemia mast cells and Jurkat T cells.
Stimulus-induced secretion of bioactive polypeptides is a fundamental aspect of the immune system. Secretory proteins are synthesized in the endoplasmic reticulum and are transported through the Golgi apparatus to the trans-Golgi network, where they are sorted into transport vesicles that bud off and fuse into condensing vacuoles, which subsequently undergo an editing and concentration process to become mature secretory vesicles. In this study, we report that the PTP-MEG2 protein tyrosine phosphatase is located on these vesicles in mast cells. Expression of PTP-MEG2 caused a striking enlargement of these vesicles in both rat basophilic leukemia mast cells and Jurkat T leukemia cells into giant vesicles with diameters of up to several micrometers. The fused vesicles did not acquire markers for other compartments and were adjacent to the trans-Golgi network, contained carboxypeptidase E, chromogranin C, and IL-2, and had an electron-dense core typical of secretory vesicles. Expression of PTP-MEG2 also caused a reduction in the secretion of IL-2 from stimulated Jurkat cells. The effects of PTP-MEG2 on secretory vesicles required the catalytic activity of PTP-MEG2 and was rapidly reversed by pervanadate. We propose that PTP-MEG2 represents a novel connection between tyrosine dephosphorylation and the regulation of secretory vesicles in hematopoietic cells.
Wang
Xiaodong
X
Program of Signal Transduction, Cancer Research Center, The Burnham Institute, La Jolla, CA 92037, USA.
Huynh
Huong
H
Gjörloff-Wingren
Anette
A
Monosov
Edvard
E
Stridsberg
Mats
M
Fukuda
Minoru
M
Mustelin
Tomas
T
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002478:Cells, Cultured; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D019169:Jurkat Cells; D015471:Leukemia, Basophilic, Acute; D008407:Mast Cells / Q000201:enzymology* / Q000276:immunology / Q000648:ultrastructure; D008561:Membrane Fusion; D017027:Protein Tyrosine Phosphatases / Q000032:analysis / Q000502:physiology*; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D051381:Rats; D022142:Secretory Vesicles / Q000201:enzymology* / Q000648:ultrastructure*; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology / Q000648:ultrastructure; D014407:Tumor Cells, Cultured
D015415:Biomarkers; D007376:Interleukin-2; C447615:PTPN9 protein, human; D017027:Protein Tyrosine Phosphatases; D054558:Protein Tyrosine Phosphatases, Non-Receptor