scholarly journals Surface expression of a heterologous phosphatase complements CD45 deficiency in a T cell clone.

1994 ◽  
Vol 180 (4) ◽  
pp. 1359-1366 ◽  
Author(s):  
D G Motto ◽  
M A Musci ◽  
G A Koretzky
Keyword(s):  
Signal Transduction ◽  
T Cell ◽  
Cell Line ◽  
Inositol Phosphate ◽  
Tyrosine Phosphatase ◽  
Surface Expression ◽  
Transmembrane Domains ◽  
Lymphoid Cells ◽  
Protein Tyrosine ◽  
T Cell Clone

Expression of CD45, the major transmembrane protein tyrosine phosphatase expressed on lymphoid cells, is required for optimal T cell receptor (TCR) signal transduction. We and others recently have demonstrated that surface expression of the cytoplasmic domain of CD45 in the absence of its extracellular and transmembrane domains is sufficient to restore TCR-mediated signaling events in CD45-deficient cell lines. Here we demonstrate that a single domain nonreceptor tyrosine phosphatase from yeast expressed as a chimeric protein with the extracellular and transmembrane domains of a major histocompatibility complex class I molecule also is able to restore proximal and distal TCR-mediated signal transduction events in the CD45-deficient T cell line J45.01. Ligation of the TCR on the cell line expressing the yeast phosphatase chimera results in the induction of protein tyrosine kinase activity, soluble inositol phosphate generation, and expression of the CD69 activation antigen. Furthermore, a phosphatase-inactive version of this molecule is unable to restore signal transduction, providing the first formal evidence that plasma membrane associated tyrosine phosphatase activity is required for TCR-mediated signaling.

scholarly journals Loss of T-Cell Protein Tyrosine Phosphatase Induces Recycling of the Platelet-derived Growth Factor (PDGF) β-Receptor but Not the PDGF α-Receptor

2006 ◽  
Vol 17 (11) ◽  
pp. 4846-4855 ◽  
Author(s):  
Susann Karlsson ◽  
Katarzyna Kowanetz ◽  
Åsa Sandin ◽  
Camilla Persson ◽  
Arne Östman ◽  
...  
Keyword(s):  
T Cell ◽  
Growth Factor ◽  
Cell Surface ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Dominant Negative ◽  
Platelet Derived Growth Factor ◽  
Cell Protein ◽  
Protein Tyrosine ◽  
Β Receptor

We have previously shown that the T-cell protein tyrosine phosphatase (TC-PTP) dephosphorylates the platelet-derived growth factor (PDGF) β-receptor. Here, we show that the increased PDGF β-receptor phosphorylation in TC-PTP knockout (ko) mouse embryonic fibroblasts (MEFs) occurs primarily on the cell surface. The increased phosphorylation is accompanied by a TC-PTP–dependent, monensin-sensitive delay in clearance of cell surface PDGF β-receptors and delayed receptor degradation, suggesting PDGF β-receptor recycling. Recycled receptors could also be directly detected on the cell surface of TC-PTP ko MEFs. The effect of TC-PTP depletion was specific for the PDGF β-receptor, because PDGF α-receptor homodimers were cleared from the cell surface at the same rate in TC-PTP ko MEFs as in wild-type MEFs. Interestingly, PDGF αβ-receptor heterodimers were recycling. Analysis by confocal microscopy revealed that, in TC-PTP ko MEFs, activated PDGF β-receptors colocalized with Rab4a, a marker for rapid recycling. In accordance with this, transient expression of a dominant-negative Rab4a construct increased the rate of clearance of cell surface receptors on TC-PTP ko MEFs. Thus, loss of TC-PTP specifically redirects the PDGF β-receptor toward rapid recycling, which is the first evidence of differential trafficking of PDGF receptor family members.

scholarly journals Polyunsaturated Fatty Acids Inhibit T Cell Signal Transduction by Modification of Detergent-insoluble Membrane Domains

1998 ◽  
Vol 143 (3) ◽  
pp. 637-644 ◽  
Author(s):  
Thomas M. Stulnig ◽  
Markus Berger ◽  
Thomas Sigmund ◽  
Daniel Raederstorff ◽  
Hannes Stockinger ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Fatty Acids ◽  
T Cells ◽  
T Cell ◽  
Polyunsaturated Fatty Acids ◽  
Membrane Domains ◽  
Protein Tyrosine ◽  
Cell Signal ◽  
Family Protein ◽  
Cell Signal Transduction

Polyunsaturated fatty acids (PUFAs) exert immunosuppressive effects, but the molecular alterations leading to T cell inhibition are not yet elucidated. Signal transduction seems to involve detergent-resistant membrane domains (DRMs) acting as functional rafts within the plasma membrane bilayer with Src family protein tyrosine kinases being attached to their cytoplasmic leaflet. Since DRMs include predominantly saturated fatty acyl moieties, we investigated whether PUFAs could affect T cell signaling by remodeling of DRMs. Jurkat T cells cultured in PUFA-supplemented medium showed a markedly diminished calcium response when stimulated via the transmembrane CD3 complex or glycosyl phosphatidylinositol (GPI)- anchored CD59. Immunofluorescence studies indicated that CD59 but not Src family protein tyrosine kinase Lck remained in a punctate pattern after PUFA enrichment. Analysis of DRMs revealed a marked displacement of Src family kinases (Lck, Fyn) from DRMs derived from PUFA-enriched T cells compared with controls, and the presence of Lck in DRMs strictly correlated with calcium signaling. In contrast, GPI-anchored proteins (CD59, CD48) and ganglioside GM1, both residing in the outer membrane leaflet, remained in the DRM fraction. In conclusion, PUFA enrichment selectively modifies the cytoplasmic layer of DRMs and this alteration could underlie the inhibition of T cell signal transduction by PUFAs.

scholarly journals The YRD Motif Is a Major Determinant of Substrate and Inhibitor Specificity in T-cell Protein-tyrosine Phosphatase

2001 ◽  
Vol 276 (28) ◽  
pp. 26036-26043 ◽  
Author(s):  
Ernest Asante-Appiah ◽  
Kristen Ball ◽  
Kevin Bateman ◽  
Kathryn Skorey ◽  
Rick Friesen ◽  
...  
Keyword(s):  
T Cell ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Major Determinant ◽  
Cell Protein ◽  
Inhibitor Specificity ◽  
Protein Tyrosine ◽  
The Yrd

Streptococcus sanguis-induced platelet activation involves two waves of tyrosine phosphorylation mediated by FcγRIIA and αIIbβ3

2005 ◽  
Vol 93 (05) ◽  
pp. 932-939 ◽  
Author(s):  
Caroline Pampolina ◽  
Archibald McNicol
Keyword(s):  
Signal Transduction ◽  
Platelet Aggregation ◽  
Tyrosine Phosphorylation ◽  
Platelet Activation ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine Phosphatases ◽  
Lag Phase ◽  
Dependent Manner ◽  
Protein Tyrosine ◽  
Streptococcus Sanguis

SummaryThe low-affinity IgG receptor, FcγRIIA, has been implicated in Streptococcus sanguis-induced platelet aggregation. Therefore, it is likely that signal transduction is at least partly mediated by FcγRIIA activation and a tyrosine kinase-dependent pathway. In this study the signal transduction mechanisms associated with platelet activation in response to the oral bacterium, S. sanguis were characterised. In the presence of IgG, S. sanguis strain 2017–78 caused the tyrosine phosphorylation of FcγRIIA 30s following stimulation, which led to the phosphorylation of Syk, LAT, and PLCγ2. These early events were dependent on Src family kinases but independent of either TxA2 or the engagement of the αIIbβ3 integrin. During the lag phase prior to platelet aggregation, FcγRIIA, Syk, LAT, and PLCγ2 were each dephosphorylated, but were re-phosphorylated as aggregation occurred. Platelet stimulation by 2017–78 also induced the tyrosine phosphorylation of PECAM-1, an ITIM-containing receptor that recruits protein tyrosine phosphatases. PECAM-1 co-precipitated with the protein tyrosine phosphatase SHP-1 in the lag phase. SHP-1 was also maximally tyrosine phosphorylated during this phase, suggesting a possible role for SHP-1 in the observed dephosphorylation events. As aggregation occurred, SHP-1 was dephosphorylated, while FcγRIIA, Syk, LAT, and PLCγ2 were rephosphorylated in an RGDS-sensitive, and therefore αIIbβ3-dependent, manner. Additionally, TxA2 release, 5-hydro-xytryptamine secretion and phosphatidic acid formation were all blocked by RGDS. Aspirin also abolished these events, but only partially inhibited αIIbβ3-mediated re-phosphorylation. Therefore, S.sanguis-bound IgG cross links FcγRIIA and initiates a signaling pathway that is down-regulated by PECAM-1-bound SHP-1. Subsequent engagement of αIIbβ3 leads to SHP-1 dephosphorylation permiting a second wave of signaling leading to TxA2 release and consequent platelet aggregation.

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