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961.
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Anna S. Tocheva Michael Peled Marianne Strazza Kieran R. Adam Shalom Lerrer Shruti Nayak Inbar Azoulay-Alfaguter Connor J.R. Foster Elliot A. Philips Benjamin G. Neel Beatrix Ueberheide Adam Mor 《The Journal of biological chemistry》2020,295(52):18036
Programmed cell death protein 1 (PD-1) is a critical inhibitory receptor that limits excessive T cell responses. Cancer cells have evolved to evade these immunoregulatory mechanisms by upregulating PD-1 ligands and preventing T cell–mediated anti-tumor responses. Consequently, therapeutic blockade of PD-1 enhances T cell–mediated anti-tumor immunity, but many patients do not respond and a significant proportion develop inflammatory toxicities. To improve anti-cancer therapy, it is critical to reveal the mechanisms by which PD-1 regulates T cell responses. We performed global quantitative phosphoproteomic interrogation of PD-1 signaling in T cells. By complementing our analysis with functional validation assays, we show that PD-1 targets tyrosine phosphosites that mediate proximal T cell receptor signaling, cytoskeletal organization, and immune synapse formation. PD-1 ligation also led to differential phosphorylation of serine and threonine sites within proteins regulating T cell activation, gene expression, and protein translation. In silico predictions revealed that kinase/substrate relationships engaged downstream of PD-1 ligation. These insights uncover the phosphoproteomic landscape of PD-1–triggered pathways and reveal novel PD-1 substrates that modulate diverse T cell functions and may serve as future therapeutic targets. These data are a useful resource in the design of future PD-1–targeting therapeutic approaches. 相似文献
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Channa Sunita Lavis Anna Connor Charlotte Palmer Colin Leung Newman Birchwood Max 《Culture, medicine and psychiatry》2019,43(3):361-386
Culture, Medicine, and Psychiatry - Eating disorder diagnoses are characterised by a pattern of disordered eating behaviour alongside symptoms such as body dissatisfaction and preoccupation with... 相似文献
967.
Cody J. Dey Constance M. OConnor Holly Wilkinson Susanne Shultz Sigal Balshine John L Fitzpatrick 《Ethology : formerly Zeitschrift fur Tierpsychologie》2019,125(6):409-414
In 2017, we demonstrated that transitions to cooperative breeding in Lamprologine cichlid fishes were not related to a species’ social mating system (Dey et al. 2017. Nature Ecology & Evolution, 1 , 137). This contrasted previous evidence that monogamy (and a low degree of promiscuity) promoted transitions to cooperative breeding in other taxa. Recently, Tanaka et al. (2018. Ethology, 124 , 777–789) critiqued our study and argued that a re‐analysis of the data shows transitions to cooperative breeding are promoted by non‐monogamous mating systems. Here, we show that Tanaka et al.'s critique contains numerous inaccuracies. In addition, we show that the results put forth by Tanaka et al. emerge only under the extreme scenario in which all cooperative breeding species are classified as non‐monogamous, which we argue arises because Tanaka et al. confound social systems and mating systems. While we agree that there is uncertainty regarding the mating system of some Lamprologine species, we argue this uncertainty was sufficiently addressed through the extensive sensitivity analyses conducted in our original study. 相似文献
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Lakhena Leang Molly C. McDonald Charlotte R. Mineo Brandon Jones Travis Barker Connor Gagliardi Kristin M. Fox 《Biochemistry and Biophysics Reports》2019
The role of programmed cell death in filamentous fungi is not well-understood, but is important due to the role of fungi in opportunistic infections. Plants, fungi and protozoa do not have caspase genes, but instead express the homologous proteins denoted metacaspases. To better understand the role of metacaspases in fungi we present an analysis of the sequences and activities of all five Type I metacaspases from Schizophyllum commune (ScMC), a mushroom-forming basiodmycete that undergoes sexual reproduction. The five Type I metacaspases of S. commune can be divided into two groups based on sequence similarity. Enzymes both with and without the N-terminal prodomain are active, but here we report on the constructs without the prodomains (Δpro). All five ScMCΔpro proteins show the highest enzymatic activity between pH 7 and 8 and require calcium for optimal activity. Optimal Ca2+ concentrations for ScMC1Δpro and ScMC2Δpro are 50 mM, while ScMC3, ScMC4Δpro and ScMC5Δpro activity is optimal around 5 mM calcium. All five S. commune metacaspases have similar substrate specificity. They are most active with Arg in the P1 position and inactive with Asp in the P1 position. 相似文献
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Maged1, a new regulator of skeletal myogenic differentiation and muscle regeneration 总被引:1,自引:0,他引:1
Tuan HN Nguyen Mathieu JM Bertrand Christiane Sterpin Younes Achouri Olivier RY De Backer 《BMC cell biology》2010,11(1):57