scholarly journals Determination of the non-ionic detergent insolubility and phosphoprotein associations of glycosylphosphatidylinositol-anchored proteins expressed on T cells

1998 ◽  
Vol 334 (2) ◽  
pp. 325-333 ◽  
Author(s):  
Keith R. SOLOMON ◽  
Mark A. MALLORY ◽  
Robert W. FINBERG
Keyword(s):  
Signal Transduction ◽  
T Cells ◽  
Tyrosine Kinases ◽  
Activated T Cells ◽  
Lipid Microdomains ◽  
Signalling Molecules ◽  
Ionic Detergent ◽  
Src Family Tyrosine Kinases ◽  
Haemopoietic Cells ◽  
Triton X

Glycosylphosphatidylinositol (GPI)-anchored proteins are poorly solublized in non-ionic detergents such as Triton X-100 and Nonidet P40, but are easily solublized by detergents with high critical micelle concentrations such as octylglucoside. This solubility profile has been suggested to be due to the localization of GPI-anchored proteins to lipid microdomains rich in cholesterol and sphingolipids. Additionally, GPI-anchored proteins expressed on haemopoietic cells have been shown to associate with src-family tyrosine kinases and heterotrimeric G proteins. Despite these observations, the non-ionic detergent insolubility of GPI-anchored proteins on haemopoietic cells has not been quantified nor has a relationship between the non-ionic detergent insolubility of these proteins and their association with signal-transduction molecules been identified. Here we show that GPI-anchored proteins found on T-cell tumours and activated T cells, although significantly more insoluble then transmembrane proteins, are not uniform in their detergent insolubility. Whereas CD59 was between 4% and 13% soluble, CD48 was between 13% and 25% soluble, CD55 was between 20% and 30% soluble, and CD109 was between 34% and 75% soluble. The ability of these GPI-anchored proteins to associate with phosphoproteins was correlated with their detergent insolubility: the more detergent-insoluble that a GPI-anchored protein was, the greater the level of phosphoprotein associations. These experiments reveal a relationship between non-ionic detergent insolubility and association with signal-transduction molecules and suggest a cause-and-effect relationship between these two properties. In total, these experiments support the hypothesis that the association of GPI-anchored proteins with signalling molecules is due to their sorting to lipid microdomains.

scholarly journals Disruption of Lymphocyte Function and Signaling in CD45–associated Protein–null Mice

1998 ◽  
Vol 187 (11) ◽  
pp. 1863-1870 ◽  
Author(s):  
Akio Matsuda ◽  
Satoshi Motoya ◽  
Shioko Kimura ◽  
Renee McInnis ◽  
Abby L. Maizel ◽  
...  
Keyword(s):  
Signal Transduction ◽  
T Cells ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Kinases ◽  
Tyrosine Phosphatase ◽  
Antigen Receptor ◽  
Lymphocyte Function ◽  
Receptor Signaling ◽  
Protein Tyrosine ◽  
Antigen Receptor Signaling

CD45-AP specifically associates with CD45, a protein tyrosine phosphatase essential for lymphocyte differentiation and antigen receptor–mediated signal transduction. CD45 is thought to mediate antigen receptor signaling by dephosphorylating regulatory tyrosine residues on Src family protein tyrosine kinases such as Lck. However, the mechanism for regulating CD45 protein tyrosine phosphatase activity remains unclear. CD45-AP–null mice were created to examine the role of CD45-AP in CD45-mediated signal transduction. T and B lymphocytes showed reduced proliferation in response to antigen receptor stimulation. Both mixed leukocyte reaction and cytotoxic T lymphocyte functions of T cells were also markedly decreased in CD45-AP–null mice. Interestingly, the interaction between CD45 and Lck was significantly reduced in CD45-AP–null T cells, indicating that CD45-AP directly or indirectly mediates the interaction of CD45 with Lck. Our data indicate that CD45-AP is required for normal antigen receptor signaling and function in lymphocytes.

PKCθ-regulated signalling in health and disease

2014 ◽  
Vol 42 (6) ◽  
pp. 1484-1489 ◽  
Author(s):  
Pulak R. Nath ◽  
Noah Isakov
Keyword(s):  
Signal Transduction ◽  
T Cells ◽  
T Cell ◽  
Immunological Synapse ◽  
Cell Types ◽  
Cell Receptor ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
Health And Disease

Protein kinase Cθ (PKCθ) is a key enzyme in T-lymphocytes where it plays an important role in signal transduction downstream of the activated T-cell receptor (TCR) and the CD28 co-stimulatory receptor. Antigenic stimulation of T-cells triggers PKCθ translocation to the centre of the immunological synapse (IS) at the contact site between antigen-specific T-cells and antigen-presenting cells (APCs). The IS-residing PKCθ phosphorylates and activates effector molecules that transduce signals into distinct subcellular compartments and activate the transcription factors, nuclear factor κB (NF-κB), nuclear factor of activated T-cells (NFAT) and activating protein 1 (AP-1), which are essential for the induction of T-cell-mediated responses. Besides its major biological role in T-cells, PKCθ is expressed in several additional cell types and is involved in a variety of distinct physiological and pathological phenomena. For example, PKCθ is expressed at high levels in platelets where it regulates signal transduction from distinct surface receptors, and is required for optimal platelet activation and aggregation, as well as haemostasis. In addition, PKCθ is involved in physiological processes regulating insulin resistance and susceptibility to obesity, and is expressed at high levels in gastrointestinal stromal tumours (GISTs), although the functional importance of PKCθ in these processes and cell types is not fully clear. The present article briefly reviews selected topics relevant to the biological roles of PKCθ in health and disease.

W2 3:50 Signal transduction and gene expression in activated T cells from old donors

1997 ◽  
Vol 21 (2) ◽  
pp. 251
Author(s):  
W.H. Adler ◽  
L.J. Song ◽  
P.D. Baskar ◽  
G.D. Collins ◽  
F.J. Chrest ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signal Transduction ◽  
T Cells ◽  
Activated T Cells

scholarly journals Platelet αIIb-β3 integrin engagement induces the tyrosine phosphorylation of Cbl and its association with phosphoinositide 3-kinase and Syk

2000 ◽  
Vol 351 (3) ◽  
pp. 669-676 ◽  
Author(s):  
Abdelhafid SACI ◽  
Francine RENDU ◽  
Christilla BACHELOT-LOZA
Keyword(s):  
Signal Transduction ◽  
Platelet Aggregation ◽  
Tyrosine Phosphorylation ◽  
Platelet Activation ◽  
Tyrosine Kinases ◽  
Kinase Activity ◽  
Src Family Kinases ◽  
Β3 Integrin ◽  
Phosphoinositide 3 Kinase ◽  
Src Family Tyrosine Kinases

Agonist-induced platelet activation triggers ‘inside-out’signalling which activates αIIb-β3, the most abundant integrin in platelet membranes. The engagement of activated αIIb-β3 integrin by linking fibrinogen is necessary for platelet aggregation, and this induces subsequent outside-in signalling, which enhances platelet activation. Here we studied the involvement of Cbl during αIIb-β3-integrin-mediated signal transduction. During thrombin-induced platelet activation, Cbl was tyrosine phosphorylated, and phosphoinositide 3-kinase (PI 3-kinase) activity measured in Cbl immunoprecipitates was increased. Both Cbl phosphorylation and its association with PI 3-kinase were dependent on αIIb-β3 engagement by linking fibrinogen. The P256 and anti-LIBS6 (ligand-induced binding site 6) antibodies, which activate platelets directly through αIIb-β3, induced Cbl phosphorylation and increased the PI 3-kinase activity associated with Cbl. Both thrombin and antibodies to αIIb-β3 induced association of Cbl with the tyrosine kinase, Syk. Experiments performed with inhibitors of tyrosine kinases indicated that both Src-family kinases and Syk contribute to phosphorylation of Cbl and its consequent association with PI 3-kinase. The results show that, following integrin αIIb-β3 engagement, Cbl is tyrosine phosphorylated, recruits PI 3-kinase to this integrin signalling pathway and possibly enhances PI 3-kinase activity, downstream of Src-family tyrosine kinases and Syk activation.

scholarly journals Receptor-induced death in human natural killer cells: involvement of CD16.

1995 ◽  
Vol 181 (1) ◽  
pp. 339-344 ◽  
Author(s):  
J R Ortaldo ◽  
A T Mason ◽  
J J O'Shea
Keyword(s):  
T Cells ◽  
Cell Death ◽  
Nk Cells ◽  
Natural Killer ◽  
Tyrosine Kinases ◽  
Nk Cell ◽  
Interleukin 2 ◽  
Activated T Cells ◽  
Human Natural Killer Cells ◽  
Induced Apoptosis

Propriocidal regulation of T cells refers to apoptosis induced by interleukin 2 (IL-2) activation with subsequent antigen receptor stimulation. We examined whether natural killer (NK) cells exhibited cytokine- and ligand-induced death similar to activated T cells. Peripheral NK cells were examined for ligand-induced death using antibodies to surface moieties (CD2, CD3, CD8, CD16, CD56), with and without prior activation of IL-2. Only those NK cells stimulated first with IL-2 and then with CD16 exhibited ligand-induced death; none of the other antibody stimuli induced this phenomenon. Next we examined various cytokines (IL-2, IL-4, IL-6, IL-7, IL-12, IL-13, interferon alpha and gamma) that can activate NK cells and determined if CD16-induced killing occurred. Only IL-2 and IL-12 induced NK cell death after occupancy of this receptor by aggregated immunoglobulin or by cross-linking with antireceptor antibody. The CD16-induced death was inhibited by herbimycin A, indicating that cell death was dependent upon protein tyrosine kinases. Identical to T cells, the form of cell death for NK cells was demonstrated to be receptor-induced apoptosis. Overall these data indicate that highly activated NK cells mediate ligand-induced apoptosis via signaling molecules like CD16. Whereas the propriocidal regulation of T cells is antigen specific, this is not the case for NK cells due to the nature of the receptor. The clinical implications of this finding are considered.

Signal transduction by HLA class II antigens expressed on activated T cells

1991 ◽  
Vol 21 (1) ◽  
pp. 123-129 ◽  
Author(s):  
Niels Ødum ◽  
Paul J. Martin ◽  
Gary L. Schieven ◽  
John A. Hansen ◽  
Jeffrey A. Ledbetter
Keyword(s):  
Signal Transduction ◽  
T Cells ◽  
Class Ii ◽  
Hla Class Ii ◽  
Activated T Cells ◽  
Class Ii Antigens

Src family tyrosine kinases in signal transduction and growth control

2001 ◽  
Vol 29 (3) ◽  
pp. A45-A45
Author(s):  
S. A. Courtneidge ◽  
C. Abram ◽  
R. Blake ◽  
M. Broome ◽  
X. Liu ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Tyrosine Kinases ◽  
Growth Control ◽  
Src Family Tyrosine Kinases

scholarly journals T cells from late tumor-bearing mice express normal levels of p56lck, p59fyn, ZAP-70, and CD3 zeta despite suppressed cytolytic activity.

1995 ◽  
Vol 182 (4) ◽  
pp. 1029-1036 ◽  
Author(s):  
D L Levey ◽  
P K Srivastava
Keyword(s):  
Signal Transduction ◽  
T Cells ◽  
Body Weight ◽  
T Cell ◽  
Tyrosine Kinases ◽  
Total Body Weight ◽  
Cytolytic Activity ◽  
The Body ◽  
Related Phenomenon ◽  
Tumor Bearing

Loss of T cell-associated signal transduction molecules has recently been implicated in immune suppression in tumor-bearing hosts. In the present study, we have examined this and related phenomenon extensively in a large number of tumor-bearing mice, analyzed individually. Splenic T cells from tumor-bearing mice were isolated and characterized with respect to the following: (a) levels of three tyrosine kinases, p56lck, p59fyn, and ZAP-70; (b) expression of CD3-zeta; (c) alloreactive responses; and (d) antigen-specific responses. Contrary to recent reports, T cells from tumor-bearing mice were observed to express normal levels of lck, fyn, ZAP-70, and CD3-zeta. Further, T cells showed healthy alloreactive and antigen-specific responses until approximately 3 wk after post tumor challenge, when the tumors constituted approximately 20% of the body weight. Alterations with respect to some parameters were observed only in mice that had been bearing larger tumors for a considerably longer period. As human tumors are unlikely to grow to such large sizes (e.g., > 20% of the total body weight), the significance of the alterations in T cell expression of lck, fyn, ZAP-70, or CD3-zeta in the immune status of cancer patients is unclear. Altogether, these results indicate that alterations in T cell signal transduction molecules do not account for the profound tumor-specific suppression observed during tumor growth.

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