Editorial Material
Biochemistry & Molecular Biology
Magalie Dosset, Maurizio Zanetti
Summary: Disulfiram, a drug commonly used for alcohol use disorders, has been repurposed for cancer treatment and plays a role in cancer immunotherapy by directly binding to Lck to activate tumor-infiltrating T cells.
Article
Biology
Yi-Chun Kao, Yi-Wen Chang, Charles P. Lai, Nai-Wen Chang, Chen-Hao Huang, Chien-Sheng Chen, Hsuan-Cheng Huang, Hsueh-Fen Juan
Summary: This study reveals that cancer cells express higher levels of eATP synthase under starvation stress, leading to increased production of EVs. The eATP synthase generates extracellular ATP to stimulate EV secretion by enhancing P2X(7) receptor-triggered Ca2+ influx. Surprisingly, eATP synthase is also found on the surface of tumor-secreted EVs. The eATP synthase-coated EVs increase uptake by immune cells and inhibit their proliferation and cytokine release.
COMMUNICATIONS BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Kaitao Li, Zhou Yuan, Jintian Lyu, Eunseon Ahn, Simon J. Davis, Rafi Ahmed, Cheng Zhu
Summary: The study reveals that PD-1 inhibits the cooperative interaction between TCR-pMHC-CD8 by suppressing TCR proximal signaling, leading to reduced antigen recognition by T cells.
NATURE COMMUNICATIONS
(2021)
Article
Immunology
Nikolaos Koutras, Vasileios Morfos, Kyriakos Konnaris, Adamantia Kouvela, Athanasios-Nasir Shaukat, Constantinos Stathopoulos, Vassiliki Stamatopoulou, Konstantina Nika
Summary: This study reveals the ectopic function of SFKs in B cells and compares it to the predominant B cell SFK, Lyn. Our findings show substrate promiscuity displayed by these two SFKs, which is regulated by different mechanisms. Moreover, we demonstrate that signals generated by Lck and Lyn are sufficient to induce transcriptome alterations in B cells, resembling B cell activation. Additionally, we uncover a previously unknown role of SFKs in tipping the balance of cellular stress responses in B lymphocytes.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Cell Biology
Ling Wu, Joanna Brzostek, Previtha Dawn Sakthi Vale, Qianru Wei, Clara K. T. Koh, June Xu Hui Ong, Liang-zhe Wu, Jia Chi Tan, Yen Leong Chua, Jiawei Yap, Yuan Song, Vivian Jia Yi Tan, Triscilla Y. Y. Tan, Junyun Lai, Paul A. MacAry, Nicholas R. J. Gascoigne
Summary: This study reveals that chimeric antigen receptor (CAR) signaling can occur independently of the SRC family kinase (SFK) LCK and instead relies on FYN and a CD28 intracellular domain within the CAR. LCK-deficient CAR-T cells exhibit stronger signaling through CAR and show improved in vivo efficacy with reduced exhaustion phenotype and enhanced induction of memory and proliferation. These findings provide insights into the initiation of both T cell receptor (TCR) and CAR signaling and have important clinical implications for improving CAR function.
CELL REPORTS MEDICINE
(2023)
Article
Neurosciences
Vishaal Rajani, Ameet S. Sengar, Michael W. Salter
Summary: SFKs are crucial non-receptor tyrosine kinases in multiple signalling pathways, playing a key role in regulating NMDAR function and neuronal transduction pathways. Src and Fyn members of SFKs are essential for inducing plasticity at hippocampal synapses, while aberrant regulation of NMDARs by SFKs is implicated in diseases like schizophrenia and pain hypersensitivity. The targeting of SFK protein-protein interactions could be a potential therapeutic strategy for restoring glutamatergic dysregulation in CNS disease pathophysiology.
Article
Immunology
Xiang Zhao, Liang-Zhe Wu, Esther K. Y. Ng, Kerisa W. S. Leow, Qianru Wei, Nicholas R. J. Gascoigne, Joanna Brzostek
Summary: Co-agonist pMHC class I complexes recruit CD8-bound Lck to the immune synapse to modulate CD8(+) T cell signaling pathways, enhancing effector functions and proliferation. Furthermore, co-agonism can boost T cell proliferation through an extrinsic mechanism, priming neighboring CD8(+) T cells for enhanced Akt pathway activation and proliferation.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Deborah K. Johnson, Wyatt Magoffin, Sheldon J. Myers, Jordan G. Finnell, John C. Hancock, Taylor S. Orton, Stephen P. Persaud, Kenneth A. Christensen, K. Scott Weber
Summary: CD4(+) T cells are important for suppressing and eliminating cancer cells, and their activation is influenced by CD4 expression and TCR affinity. The coreceptor CD4 inhibits TCR activation through various mechanisms. TCR-pMHCII affinity and construct format impact IL-2 production and tetramer staining for each TCR.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Richard M. Powell, Marlies J. W. Peeters, Anne Rahbech, Pia Aehnlich, Tina Seremet, Per Thor Straten
Summary: This study investigates the impact of new generation and potent MERTK/FLT3 receptor tyrosine kinase inhibitors on human primary CD8(+) T cell function, revealing that the use of a dual MERTK/FLT3 inhibitor restricts CD8(+) T cell proliferation while largely leaving cytokine production and activation unaffected. Additionally, the study shows that activated CD8(+) T cells express FLT3 early on post-activation, and inhibition of FLT3 affects cell cycle kinetics. These results highlight the need for caution when using potent RTKIs in the context of antitumor immune responses.
Article
Cell Biology
Natalie Gindi, Hadas Grossman, Hadas Bar-Joseph, Irit Miller, Luba Nemerovsky, Ron Hadas, Nava Nevo, Dalia Galiani, Nava Dekel, Ruth Shalgi
Summary: The study revealed that Fyn/SFKs play a role in maintaining the stability of pre-transcribed mRNAs in oocytes at the GV stage, while Fyn, SFKs, and AGO2 are involved in promoting the degradation of maternal mRNAs during in-vivo oocyte maturation.
Article
Biochemistry & Molecular Biology
Qinlan Wang, Ting Zhu, Naijun Miao, Yingying Qu, Zhuning Wang, Yinong Chao, Jing Wang, Wei Wu, Xinyi Xu, Chenqi Xu, Li Xia, Feng Wang
Summary: The study demonstrates that DSF can directly activate LCK-mediated TCR signaling, promoting anti-tumor response of CD8(+) T cells and enhancing effector T cell function and proliferation, providing novel insights into the therapeutic effect of DSF on cancer.
Article
Biochemical Research Methods
Xien Yu Chua, Timothy Aballo, William Elnemer, Melanie Tran, Arthur Salomon
Summary: The study revealed a dynamic Lck protein interaction network in living T cells after TCR stimulation using TurboID technology. This novel application demonstrated the potential of TurboID to unveil Lck interactions associated with cell signaling and immune response.
JOURNAL OF PROTEOME RESEARCH
(2021)
Article
Multidisciplinary Sciences
Wen Lu, Katarzyna M. Skrzypczynska, Arthur Weiss
Summary: Src-family kinases play different roles in T cell and B cell signaling, with their activity regulated by factors such as Csk. Csk is crucial for maintaining appropriate SFK activity levels and regulating PIP3 amounts to prevent inappropriate B cell activation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Neurosciences
Han Qiu, Tianyang Qian, Tong Wu, Ting Gao, Qinghe Xing, Laishuan Wang
Summary: This study identified the pattern of p-Src expression after HI brain injury in immature rats and demonstrated its relationship with activated NMDA receptors. Inhibiting p-Src can ameliorate neuropathological changes and damage to neurological functions induced by HI injury.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Review
Cell Biology
Fang Du, Tao Tang, Qingzhu Li, Jiaxin Liu
Summary: Ischemic stroke is a common type of stroke that causes disability and death. Fyn, a nonreceptor tyrosine kinase, plays a crucial role in the pathological processes of cerebral ischemia-reperfusion, including energy metabolism disorders, neurotoxicity, and apoptotic gene activation. Fyn also promotes the production of superoxide, contributing to cerebral ischemia-reperfusion injury. Exploring the role of Fyn is important for understanding the mechanisms of cerebral ischemia-reperfusion injury and developing treatment strategies.
MEDIATORS OF INFLAMMATION
(2022)
Article
Immunology
Julio M. Rubio, Alma M. Astudillo, Javier Casas, Maria A. Balboa, Jesus Balsinde
FRONTIERS IN IMMUNOLOGY
(2018)
Article
Biochemistry & Molecular Biology
Lise Boon, Estefania Ugarte-Berzal, Erik Martens, Jennifer Vandooren, Vasily Rybakin, Didier Colau, Monica Gordon-Alonso, Pierre van der Bruggen, Walter Stoecker, Christoph Becker-Pauly, Peter Witters, Eva Morava, Jaak Jaeken, Paul Proost, Ghislain Opdenakker
Article
Cell Biology
Adrian Boey, Vasily Rybakin, Dharamdajal Kalicharan, Katlijn Vints, Natalia V. Gounko
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY
(2019)
Article
Multidisciplinary Sciences
Katlijn Vints, Dorien Vandael, Pieter Baatsen, Benjamin Pavie, Frank Vernaillen, Nikky Corthout, Vasily Rybakin, Sebastian Munck, Natalia Gounko
SCIENTIFIC REPORTS
(2019)
Article
Multidisciplinary Sciences
Elijah W. Chen, Chyan Ying Ke, Joanna Brzostek, Nicholas R. J. Gascoigne, Vasily Rybakin
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2019)
Article
Gastroenterology & Hepatology
Janette Furuzawa-Carballeda, Lise Boon, Gonzalo Torres-Villalobos, Fernanda Romero-Hernandez, Estefania Ugarte-Berzal, Erik Martens, Jennifer Vandooren, Vasily Rybakin, Enrique Coss-Adame, Miguel Valdovinos, David Velazquez-Fernandez, Ghislain Opdenakker
CLINICAL AND TRANSLATIONAL GASTROENTEROLOGY
(2018)
Article
Biochemistry & Molecular Biology
Vasily Rybakin, Melissa Stas, Estefania Ugarte-Berzal, Sam Noppen, Jennifer Vandooren, Ilse Van Aelst, Sandra Liekens, Paul Proost, Ghislain Opdenakker
BIOCHEMICAL JOURNAL
(2019)
Article
Immunology
Elijah W. Chen, Neil Q. Tay, Joanna Brzostek, Nicholas R. J. Gascoigne, Vasily Rybakin
FRONTIERS IN IMMUNOLOGY
(2019)
Article
Immunology
Joanna Brzostek, Namrata Gautam, Xiang Zhao, Elijah W. Chen, Monika Mehta, Desmond W. H. Tung, Yen Leong Chua, Jiawei Yap, Su H. Cho, Shvetha Sankaran, Vasily Rybakin, Guo Fu, Nicholas R. J. Gascoigne
Article
Multidisciplinary Sciences
Qianru Wei, Joanna Brzostek, Shvetha Sankaran, Javier Casas, Lois Shi-Qi Hew, Jiawei Yap, Xiang Zhao, Lukasz Wojciech, Nicholas R. J. Gascoigne
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Biochemistry & Molecular Biology
Javier Casas, Clara Meana, Jose Ramon Lopez-Lopez, Jesus Balsinde, Maria A. Balboa
Summary: This study reveals the activation of the TRPC3 channel during macrophage exposure to LPS, which is essential for intracellular Ca2+ release. TRPC3 participates in cytosolic Ca2+ elevations, NF-kappa B activation, and cytokine upregulation. Pharmacological inhibition of TRPC3 reduces LPS-induced systemic inflammation in mice.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Javier Casas, Jesus Balsinde, Maria A. Balboa
Summary: Phosphorylation of IVA cytosolic phospholipase A(2)alpha is crucial for its translocation to membranes rich in phosphatidylinositol (4,5) bisphosphate. This phosphorylation process regulates the mobilization of arachidonic acid and the synthesis of prostaglandins.
Article
Biochemistry & Molecular Biology
Carlos M. Gonzalez-Casimiro, Elisa Arribas-Rodriguez, Aida Fiz-Lopez, Javier Casas, Sara Gutierrez, Pablo Telleria, Cristina Novoa, Silvia Rojo-Rello, Eduardo Tamayo, Antonio Orduna, Carlos Duenas, David Bernardo, German Perdomo
Summary: This study reveals the significance of IDE in monocytes of COVID-19 patients, showing that its surface expression is upregulated in severe cases and downregulated after hospital discharge. IDE levels are inversely correlated with insulin levels and can be affected by high glucose and insulin levels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Liang-Zhe Wu, Renu Balyan, Joanna Brzostek, Xiang Zhao, Nicholas R. J. Gascoigne
Summary: This study found that the stronger the TCR-pMHC affinity, the shorter the time required for CD8(+) T cells to commit to proliferation. The time threshold for T cell cytokine production is lower than that for cell proliferation. There is a correlation between AKT phosphorylation and T cell proliferation. The pro-inflammatory cytokine IL-15 can override the affinity-dependent features of T cell proliferation.
Article
Immunology
Estefania Ugarte-Berzal, Lise Boon, Erik Martens, Vasily Rybakin, Daniel Blockmans, Jennifer Vandooren, Paul Proost, Ghislain Opdenakker
FRONTIERS IN IMMUNOLOGY
(2019)
