T-cell receptor complex is essential for Fas signal transduction

Akimzhanov, Askar M.; Wang, Xinmin; Sun, Jiaren; Boehning, Darren

doi:10.1073/pnas.1005419107

Cited by 31 publications

(40 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lck is required for the most proximal Fas signaling events, including PLC-γ1 activation, proapoptotic calcium release, and cell death in T cells (20). Using a pulsed metabolic labeling and detection strategy, here we show that Lck palmitate turnover is very rapid even in resting T cells.…”

mentioning

confidence: 87%

“…We previously demonstrated that PLC-γ1-mediated calcium release from endoplasmic reticulum stores is required for Fas signaling (20,21). To determine whether rapid and transient palmitoylation of Lck depends on Fas-mediated elevations in cytoplasmic calcium, we used J.gamma1 (PLC-γ1 null) Jurkat cells deficient in Fasmediated calcium release (20,21). We found that basal Lck palmitoylation levels in J.gamma1 cells remained unchanged, but Fas-mediated changes in Lck palmitoylation were completely absent in this cell line (Fig.…”

Section: Fas Receptor Stimulation Leads To a Rapid And Transient Incrmentioning

confidence: 99%

“…We have previously demonstrated that Lck is an essential component of the Fas signaling pathway (20). Lck is required for the most proximal Fas signaling events, including PLC-γ1 activation, proapoptotic calcium release, and cell death in T cells (20).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Rapid and transient palmitoylation of the tyrosine kinase Lck mediates Fas signaling

Akimzhanov

Boehning

2015

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Palmitoylation is the posttranslational modification of proteins with a 16-carbon fatty acid chain through a labile thioester bond. The reversibility of protein palmitoylation and its profound effect on protein function suggest that this modification could play an important role as an intracellular signaling mechanism. Evidence that palmitoylation of proteins occurs with the kinetics required for signal transduction is not clear, however. Here we show that engagement of the Fas receptor by its ligand leads to an extremely rapid and transient increase in palmitoylation levels of the tyrosine kinase Lck. Lck palmitoylation kinetics are consistent with the activation of downstream signaling proteins, such as Zap70 and PLC-γ1. Inhibiting Lck palmitoylation not only disrupts proximal Fas signaling events, but also renders cells resistant to Fas-mediated apoptosis. Knockdown of the palmitoyl acyl transferase DHHC21 eliminates activation of Lck and downstream signaling after Fas receptor stimulation. Our findings demonstrate highly dynamic Lck palmitoylation kinetics that are essential for signaling downstream of the Fas receptor.

show abstract

mentioning

confidence: 87%

Section: Fas Receptor Stimulation Leads To a Rapid And Transient Incrmentioning

confidence: 99%

See 1 more Smart Citation

Rapid and transient palmitoylation of the tyrosine kinase Lck mediates Fas signaling

Akimzhanov

Boehning

2015

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Fas is a trans-membrane protein of tumor necrosis factor receptor superfamily (Inoue et al, 2009;Matsuda et al, 2009;Akimzhanov et al, 2010;Liedtke and Trautwein, 2012) and is expressed extensively on the cytoplasmic membrane. When Fas is bound to its ligand, the apoptotic signal may be transferred to the cells.…”

Section: Fas Expression Of Mg63 By Immunocytochemistrymentioning

confidence: 99%

Marsdenia tenacissima extract sensitizes MG63 cells to doxorubicin-induced apoptosis

et al. 2014

View full text Add to dashboard Cite

ABSTRACT. Marsdenia tenacissima extract (MTE) is a new platederived biotechnology product that is frequently used, but occasionally reported, in the field of chemotherapy. In this study, we assessed the antitumor activity and related mechanisms of MTE by various biotechnological methods. The survival rates of MG63 osteosarcoma cells treated with MTE and doxorubicin were measured, individually or jointly, and the changes in cellular shape, apoptotic rates, and Fas expression were observed. The results indicated that combination of MTE and doxorubicin up-regulated Fas expression and induced apoptosis. The survival rate of combined application of 50 mg/mL MTE and 1 µg/mL doxorubicin was significantly lower than that of the individual application (P < 0.01). Other biotechnology methods also showed an apoptosis-inducing effect of combined application that was much stronger than individual application. All of these results suggested that MTE may promote the effects of doxorubicin chemotherapy, perhaps related to the up-regulation of Fas expression in tumor cells.

show abstract

“…Fas is a kind of trans-membrane protein, belonging to the super-family of TNF receptors (Moulian and BerrihAknin, 1998;O'Callaghan et al, 2008;Inoue et al, 2009;Matsuda et al, 2009;Akimzhanov et al, 2010;Liedtke and Trautwein, 2012), and can be expressed extensively on many normal and tumor tissues. When it is ligated with Fas antibody or ligand, the apoptotic signal may be transfered into cells, and the apoptosis of cells triggered by Fas pathway may be induced.…”

Section: Discussionmentioning

confidence: 99%

Efficient Killing Effect of Osteosarcoma Cells by Cinobufacini and Cisplatin in Combination

Huang¹,

Gong²,

Li³

et al. 2012

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Purpose: To study the killing effects on osteosarcoma cells of cinobufacini and cisplatin in combination and the related mechanisms so as to explore the chemotherapeutic method with integrated traditional Chinese and Western medicines. Methods: Cinobufacini and cisplatin were applied to OS732 cells singly or jointly and survival rates were measured by MTT assay. Changes in cellular shape were observed with inverted phase contrast and fluorescence microscopy and apoptosis rates were analyzed with flow cytometry (FCM). Immunocytochemistry were used to examine the Fas expression of OS732 cells. Results: The combination of cinobufacini and cisplatin had the effect of up-regulating Fas expression and inducing apoptosis. The survival rate of combined application of 100 µg/ml cinobufacini and 1 µg/ml cisplatin on OS-732 cells was significantly lower than with either of the agents alone (p<0.01). Changes in cellular shape and apoptotic rates also indicated the apoptosis-inducing effects of combined application were much enhanced. Conclusion: The combination of cinobufacini and cisplatin demonstrated strong killing effects on OS-732 cells which might be related to up-regulation of Fas expression.

show abstract

T-cell receptor complex is essential for Fas signal transduction

Cited by 31 publications

References 31 publications

Rapid and transient palmitoylation of the tyrosine kinase Lck mediates Fas signaling

Rapid and transient palmitoylation of the tyrosine kinase Lck mediates Fas signaling

Marsdenia tenacissima extract sensitizes MG63 cells to doxorubicin-induced apoptosis

Efficient Killing Effect of Osteosarcoma Cells by Cinobufacini and Cisplatin in Combination

Contact Info

Product

Resources

About