Enlargement of Secretory Vesicles by Protein Tyrosine Phosphatase PTP-MEG2 in Rat Basophilic Leukemia Mast Cells and Jurkat T Cells

Wang, Xiaodong; Huynh, Hung; Gjörloff-Wingren, Anette; Monosov, Edvard; Stridsberg, Mats; Fukuda, Minoru; Mustelin, Tomas

doi:10.4049/jimmunol.168.9.4612

Cited by 55 publications

(58 citation statements)

References 36 publications

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“…Expression of catalytically active PTP-MEG2 results in a homotypic fusion of these normally Ͻ300-nm vesicles into giant vesicles with diameters of 1-2 m. Catalytically inactive PTP-MEG2-C515S does not cause vesicle fusion (4). When cells expressing PTP-MEG2 were stained with a mAb specific for PtdIns(3,4,5)P 3 , the resulting fluorescence was found to colocalize with PTP-MEG2 on the enlarged vesicles (Fig.…”

Section: Colocalization Of Ptp-meg2 With Ptdins(345)p 3 In Intact Cmentioning

confidence: 99%

“…PTP-MEG2 is normally found on the membrane of secretory vesicles in mast and T cells (4). Expression of catalytically active PTP-MEG2 results in a homotypic fusion of these normally Ͻ300-nm vesicles into giant vesicles with diameters of 1-2 m. Catalytically inactive PTP-MEG2-C515S does not cause vesicle fusion (4).…”

Section: Colocalization Of Ptp-meg2 With Ptdins(345)p 3 In Intact Cmentioning

confidence: 99%

“…Double immunofluorescence staining was done as before (4,24). Briefly, cells were washed in PBS and fixed in freshly made 3.7% formaldehyde.…”

Section: Confocal Microscopymentioning

confidence: 99%

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Homotypic Secretory Vesicle Fusion Induced by the Protein Tyrosine Phosphatase MEG2 Depends on Polyphosphoinositides in T Cells

Huynh

Wang²,

et al. 2003

The Journal of Immunology

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Sec14p homology domains are found in a large number of proteins from plants, yeast, invertebrates, and higher eukaryotes. We report that the N-terminal Sec14p homology domain of the human protein tyrosine phosphatase PTP-MEG2 binds phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) in vitro and colocalizes with this lipid on secretory vesicle membranes in intact cells. Point mutations that prevented PtdIns(3,4,5)P3 binding abrogated the capacity of PTP-MEG2 to induce homotypic secretory vesicle fusion in cells. Inhibition of cellular PtdIns(3,4,5)P3 synthesis also rapidly reversed the effect of PTP-MEG2 on secretory vesicles. Finally, we show that several different phosphoinositide kinases colocalize with PTP-MEG2, thus allowing for local synthesis of PtdIns(3,4,5)P3 in secretory vesicle membranes. We suggest that PTP-MEG2 through its Sec14p homology domain couples inositide phosphorylation to tyrosine dephosphorylation and the regulation of intracellular traffic of the secretory pathway in T cells.

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Section: Colocalization Of Ptp-meg2 With Ptdins(345)p 3 In Intact Cmentioning

confidence: 99%

Section: Colocalization Of Ptp-meg2 With Ptdins(345)p 3 In Intact Cmentioning

confidence: 99%

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Homotypic Secretory Vesicle Fusion Induced by the Protein Tyrosine Phosphatase MEG2 Depends on Polyphosphoinositides in T Cells

Huynh

Wang²,

et al. 2003

The Journal of Immunology

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“…Confocal Microscopy-Double immunofluorescence staining was done as described previously (28,33,34). Briefly, cells were washed in phosphate-buffered saline and fixed in freshly made 3.7% formaldehyde.…”

Section: Methodsmentioning

confidence: 99%

VHY, a Novel Myristoylated Testis-restricted Dual Specificity Protein Phosphatase Related to VHX

Narisawa

Bogetz²,

Tautz³

et al. 2004

Journal of Biological Chemistry

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The human DUSP15 gene encodes an uncharacterized 235-amino acid member of the subfamily of small dual specificity protein phosphatases related to the Vaccinia virus VH1 phosphatase. Similar to VHR-related MKPX (VHX) (DUSP22), the predicted protein has an N-terminal myristoylation recognition sequence, and we show here that both are indeed modified by the attachment of a myristate to Gly-2. In recognition of this relatedness to VHX, we refer to the DUSP15-encoded protein as VH1-related member Y (VHY). We report that VHY is expressed at high levels in the testis and barely detectable levels in the brain, spinal cord, and thyroid. A VHY-specific antiserum detected a protein with an apparent molecular mass of 26 kDa, and histochemical analysis showed that VHY was readily detectable in pachytene spermatocytes (midstage of meiotic division I) and round spermatids and weakly in Leydig cells (somatic cells outside of the seminiferous tubules). When expressed in 293T or NIH-3T3 cells, VHY was concentrated at the plasma membrane with some staining of vesicular structures in the Golgi region. Mutation of the myristoylation site Gly-2 abrogated membrane location. Finally, we demonstrate that VHY is an active phosphatase in vitro. We conclude that VHY is a new member of a subgroup of myristoylated VH1-like small dual specificity phosphatases.Phosphate is removed from phosphoproteins by several unrelated classes of protein phosphatases, including the serine/ threonine-specific phosphatases (PP1, PP2, etc.) 1 and three families of cysteine-based protein tyrosine phosphatases (PTPs) (reviewed in Refs. 1-3). There is also a newly discovered family of metal ion-dependent aspartic acid-based PTPs represented by the four Eyes Absent proteins (4 -6). The largest family of cysteine-based (7) phosphatases is made up of those related to the first sequenced PTP, PTP1B (8), and the receptor-like enzyme, CD45. Within this family are also 19 phosphatases with predominantly nonprotein substrates, 17 of them specific for the D3-phosphate of inositol phospholipids (9, 10) and two acting on RNA during the mRNA capping process (11,12). Another subgroup of 38 enzymes, referred to as the "classical" PTPs (13), have a deep catalytic pocket (ϳ9 Å), which only allows the long side chain of phosphotyrosine to reach the catalytic machinery (14). Accordingly, these PTPs are strictly tyrosine-specific. Other members of the PTP family have a more shallow catalytic pocket, and many of them dephosphorylate both phosphoserine/threonine and phosphotyrosine residues, at least in vitro (15)(16)(17)(18)(19)(20). These "dual specificity" phosphatases (DSPs) include the 11 MAP kinase phosphatases (MKPs) that dephosphorylate the mitogen-activated protein kinases Erk, Jnk, and p38 (21, 22) at their dually phosphorylated TXY activation loop motif.Another subgroup of DSPs, which we have referred to as the "atypical" DSPs (22) (as opposed to the "typical" DSPs, the MKPs), includes a number of poorly known enzymes that lack specific MAP kinase-targeting motifs and tend...

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“…23,32 Furthermore, PTP-MEG2 has been shown to be partially localized in intracellular membranes at the secretory vesicles. 32,33 In this study, we have demonstrated that PTP-MEG2 is present in both cytosol and membrane fractions of ECFCs. In PV cells, a higher level of PTP-MEG2 is located in membranes where it is highly activated.…”

Section: Discussionmentioning

confidence: 89%

PTP-MEG2 is activated in polycythemia vera erythroid progenitor cells and is required for growth and expansion of erythroid cells

Sui

Zhao

et al. 2003

Blood

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Enlargement of Secretory Vesicles by Protein Tyrosine Phosphatase PTP-MEG2 in Rat Basophilic Leukemia Mast Cells and Jurkat T Cells

Cited by 55 publications

References 36 publications

Homotypic Secretory Vesicle Fusion Induced by the Protein Tyrosine Phosphatase MEG2 Depends on Polyphosphoinositides in T Cells

Homotypic Secretory Vesicle Fusion Induced by the Protein Tyrosine Phosphatase MEG2 Depends on Polyphosphoinositides in T Cells

VHY, a Novel Myristoylated Testis-restricted Dual Specificity Protein Phosphatase Related to VHX

PTP-MEG2 is activated in polycythemia vera erythroid progenitor cells and is required for growth and expansion of erythroid cells

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