Editorial Material
Genetics & Heredity
Ivona Aksentijevich
Summary: Immune responses require a delicate balance - too weak or too strong a response can cause issues. Spleen tyrosine kinase plays a crucial role in multiple signaling pathways, and its gain-of-function alterations can lead to various problems, including hypogammaglobulinemia and predisposition to B cell lymphoma.
Article
Cell Biology
Shasha Liu, Yuan Liao, Biao Chen, Yuhai Chen, Ziding Yu, Haitao Wei, Lianfeng Zhang, Shile Huang, Paul B. Rothman, George Fu Gao, Ji-Long Chen
Summary: Research has shown that activation of STAT1 in early viral infection is not dependent on cytokines and JAKs, but mainly through Syk. Deletion of Syk profoundly impairs immediate innate immunity and suppresses the antiviral response.
Article
Biochemistry & Molecular Biology
Ji-Lin Chen, Pei-Yi Chu, Chun-Teng Huang, Tzu-Ting Huang, Wan-Lun Wang, Yu-Hsuan Lee, Yuan-Ya Chang, Ming-Shen Dai, Chung-Wai Shiau, Chun-Yu Liu
Summary: This study demonstrates that SHP-1 agonist has potent anti-tumor effects in DLBCL and may serve as a potential therapeutic drug by targeting SHP-1/p-Lyn.
MOLECULAR MEDICINE
(2022)
Article
Endocrinology & Metabolism
Adrienn Markovics, Sydney Lupo, Niyati Patel, Katalin Mikecz, D. Rick Sumner, Ryan D. Ross
Summary: This study found that Shp1 overexpression leads to increased bone mass and improved mechanical properties in mice, but only in 28-day-old mice. Female SHP1-Tg mice showed higher trabecular bone volume, trabecular number, and connectivity density compared to wildtype mice.
CALCIFIED TISSUE INTERNATIONAL
(2023)
Article
Multidisciplinary Sciences
Himangshu Sonowal, William G. Rice, Stephen B. Howell
Summary: Luxeptinib (LUX) is a novel oral kinase inhibitor that targets multiple signaling pathways and has shown promising activity in lymphoma and AML patients.
Article
Multidisciplinary Sciences
Daisuke Tsukui, Yoshitaka Kimura, Hajime Kono
Summary: Atherosclerosis complicates chronic inflammatory diseases by involving a shared physiological pathway regulated by spleen tyrosine kinase (SYK). SYK is found to be involved in atherosclerosis via the inflammatory response. Knockout of SYK gene in atherosclerosis-prone mice reduces atherosclerosis in vivo and ameliorates cell migration in macrophages. CD11c expression on SYK-knockout monocytes and macrophages is regulated by forkhead box protein O1 (FOXO1) through granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulation, mediated by c-Jun amino-terminal kinase (JNK) signaling to FOXO1. Inhibiting FOXO1 alleviates atherosclerosis in mice, suggesting GM-CSF receptor/SYK/JNK/FOXO1/CD11c signaling and FOXO1 as potential therapeutic targets for atherosclerosis and inflammatory diseases.
Article
Cell Biology
Seung Un Seo, Seon Min Woo, Taeg Kyu Kwon
Summary: This study revealed that cathepsin K inhibition activates SHP2, a tyrosine phosphatase, which dephosphorylates OTUB1 and destabilizes Raptor, leading to mitochondrial dysfunction. The findings also identified Syk as an upstream tyrosine kinase required for SHP2 activation and showed that targeting the Syk/SHP2/Src/OTUB1 axis may be a potential therapeutic strategy for cancer management.
CELL DEATH & DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Gina Perrella, Samantha J. Montague, Helena C. Brown, Lourdes Garcia Quintanilla, Alexandre Slater, David Stegner, Mark Thomas, Johan W. M. Heemskerk, Steve P. Watson
Summary: The study shows that Syk tyrosine kinase regulates the stability of thrombus under flow conditions, and this process involves pathways additional to activation of GPVI by collagen.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
John C. Kostyak, Benjamin Mauri, Carol Dangelmaier, Hymavathi Reddy Vari, Akruti Patel, Monica Wright, Haritha Reddy, Alexander Y. Tsygankov, Satya P. Kunapuli
Summary: This study demonstrates the importance of phosphorylation of Syk at Y342 in the ability of Syk to transduce a signal following activation of GPVI or CLEC-2 receptors. The Y342F mutant mice showed reduced platelet aggregation, secretion, and signaling pathways in response to agonists for GPVI or CLEC-2 receptors. Hemostasis was not affected, but thrombus formation was prolonged in these mutant mice.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Shutang Tan, Christian Luschnig, Jiri Friml
Summary: The plant hormone auxin is central to plant growth and development, with protein phosphorylation emerging as a crucial post-translational modification type regulating auxin output. This review comprehensively discusses the genetics, biochemistry, and cell biology of kinases and phosphatases involved in auxin action, providing insights into the mechanisms of developmental auxin responses and future directions for integrating protein phosphorylation control into the molecular auxin network.
Review
Biochemistry & Molecular Biology
Friederike Cuello, Friedrich W. Herberg, Konstantina Stathopoulou, Philipp Henning, Simon Diering
Summary: Pathologies such as cancer, inflammatory and cardiac diseases are often associated with long-term oxidative stress, leading to protein dysfunction and failed trials of systemic antioxidant therapy. In cardiac myocytes, cardiac contractility is mainly driven by the beta-adrenoceptor-signaling cascade activating PKA-mediated phosphorylation for positive inotropic and lusitropic effects. Both kinase and phosphatase are redox-sensitive and play crucial roles in regulating cardiac contractile function.
Article
Medicine, Research & Experimental
Tao Zhang, Suoyuan Li, Jingjie Li, Fei Yin, Yingqi Hua, Zhuoying Wang, Hongsheng Wang, Dongqing Zuo, Jing Xu, Zhengdong Cai
Summary: Pectolinarigenin inhibits STAT3 signaling, suppresses osteosarcoma growth and metastasis, and upregulates SHP-1 expression.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Review
Biochemistry & Molecular Biology
Manzar Alam, Gulam Mustafa Hasan, Md Imtaiyaz Hassan
Summary: TBK1 plays a critical role in various biological processes, with enhanced activity associated with autoimmune diseases and cancer as well as inflammatory and oncogenic processes. Recent research has highlighted the involvement of TBK1 in cancer signaling.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biochemistry & Molecular Biology
Chakrabhavi Dhananjaya Mohan, Chulwon Kim, Kodappully Sivaraman Siveen, Kanjoormana Aryan Manu, Shobith Rangappa, Arunachalam Chinnathambi, Sulaiman Ali Alharbi, Kanchugarakoppal S. Rangappa, Alan Prem Kumar, Kwang Seok Ahn
Summary: Crocetin inhibits STAT3 activation in HCC cells and affects the expression of multiple genes associated with cancer, thereby suppressing cell proliferation and invasive capacity.
Article
Biochemistry & Molecular Biology
David Maria Hollenstein, Gabriela Gerecova, Natalie Romanov, Jessica Ferrari, Jiri Veis, Marion Janschitz, Reinhard Beyer, Christoph Schueller, Egon Ogris, Markus Hartl, Gustav Ammerer, Wolfgang Reiter
Summary: This study reveals a signaling mechanism in which phosphatase-driven induction of phosphorylation occurs, with the protein phosphatase PP2A(Cdc55) acting as the main downstream effector in stress response pathways independent of kinase activation. This response affects multiple cellular processes and is crucial for stress survival. This demonstrates a previously unrecognized role of phosphatases in shaping the phosphorylome.
Article
Hematology
Ameera Alsadeq, Henning Fedders, Christian Vokuhl, Nele M. Belau, Martin Zimmermann, Tim Wirbelauer, Steffi Spielberg, Michaela Vossen-Gajcy, Gunnar Cario, Martin Schrappe, Denis M. Schewe
Article
Hematology
Ameera Alsadeq, Henning Fedders, Christian Vokuhl, Nele M. Belau, Martin Zimmermann, Tim Wirbelauer, Steffi Spielberg, Michaela Vossen-Gajcy, Gunnar Cario, Martin Schrappe, Denis M. Schewe
Letter
Hematology
Henning Fedders, Ameera Alsadeq, Juliane Schmaeh, Fotini Vogiatzi, Martin Zimmermann, Anja Moericke, Lennart Lenk, Udo zur Stadt, Martin A. Horstmann, Rob Pieters, Martin Schrappe, Martin Stanulla, Gunnar Cario, Denis M. Schewe
Article
Biochemistry & Molecular Biology
Xiaocui He, Kathrin Klaesener, Joseena M. Iype, Martin Becker, Palash C. Maity, Marco Cavallari, Peter J. Nielsen, Jianying Yang, Michael Reth
Letter
Hematology
Ameera Alsadeq, Lennart Lenk, Anila Vadakumchery, Antony Cousins, Christian Vokuhl, Ahmad Khadour, Fotini Vogiatzi, Felix Seyfried, Lueder-Hinrich Meyer, Gunnar Cario, Elias Hobeika, Klaus-Michael Debatin, Christina Halsey, Martin Schrappe, Denis M. Schewe, Hassan Jumaa
Letter
Oncology
Birgitta Christine Heckl, Michela Carlet, Binje Vick, Catrin Roolf, Ameera Alsadeq, Michaela Grunert, Wen-Hsin Liu, Andrea Liebl, Wolfgang Hiddemann, Rolf Marschalek, Denis Martin Schewe, Karsten Spiekermann, Christian Junghanss, Irmela Jeremias
LEUKEMIA & LYMPHOMA
(2019)
Article
Biology
Hannah P. Savage, Kathrin Klaesener, Fauna L. Smith, Zheng Luo, Michael Reth, Nicole Baumgarth
Review
Oncology
Lennart Lenk, Ameera Alsadeq, Denis M. Schewe
CANCER AND METASTASIS REVIEWS
(2020)
Article
Multidisciplinary Sciences
Hend Abdelrasoul, Anila Vadakumchery, Markus Werner, Lennart Lenk, Ahmad Khadour, Marc Young, Omar El Ayoubi, Fotini Vogiatzi, Markus Kraemer, Vera Schmid, Zhengshan Chen, Yasar Yousafzai, Gunnar Cario, Martin Schrappe, Markus Mueschen, Christina Halsey, Medhanie A. Mulaw, Denis M. Schewe, Elias Hobeika, Ameera Alsadeq, Hassan Jumaa
NATURE COMMUNICATIONS
(2020)
Article
Multidisciplinary Sciences
Kathrin Klaesener, Julia Jellusova, Geoffroy Andrieux, Ulrich Salzer, Chiara Boehler, Sebastian N. Steiner, Jonas B. Albinus, Marco Cavallari, Beatrix Suess, Reinhard E. Voll, Melanie Boerries, Bernd Wollscheid, Michael Reth
Summary: CD20 regulates the nanoscale organization of receptors on resting B lymphocytes, and its disruption leads to B cell activation and internalization of membrane proteins.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biology
Jennifer J. Schwarz, Lorenz Grundmann, Thomas Kokot, Kathrin Klasener, Sandra Fotteler, David Medgyesi, Maja Kohn, Michael Reth, Bettina Warscheid
Summary: This study identified and quantified human B cell signaling components using the B cell line Ramos, showing that PTP1B negatively modulates BCR signaling by dephosphorylating specific phosphotyrosines in B cell-specific receptor proteins and downstream signaling components. The study also revealed several potential substrates and binding partners of PTP1B, providing new insights into the regulation of B cell activation.
LIFE SCIENCE ALLIANCE
(2021)
Article
Oncology
Anne Charlet, Max Kappenstein, Philip Keye, Kathrin Klasener, Cornelia Endres, Teresa Poggio, Sivahari P. Gorantla, Stefanie Kreutmair, Jana Sanger, Anna L. Illert, Cornelius Miething, Michael Reth, Justus Duyster, Christoph Rummelt, Nikolas von Bubnoff
Summary: The study revealed that CSF2RB plays a role in FLT3-ITD-dependent oncogenic signaling and transformation in AML, with knockdown of CSF2RB leading to decreased STAT5 phosphorylation, attenuated cell proliferation, and increased sensitivity to FLT3 inhibition. CSF2RB is considered a rational treatment target in FLT3-ITD-positive AML based on the findings.
Article
Immunology
Alessandro Camponeschi, Kathrin Klasener, Timothy Sundell, Christina Lundqvist, Paul T. Manna, Negar Ayoubzadeh, Martina Sundqvist, Katrin Thorarinsdottir, Mariele Gatto, Marcella Visentini, Karin Onnheim, Alaitz Aranburu, Huamei Forsman, Olov Ekwall, Linda Fogelstrand, Inger Gjertsson, Michael Reth, Inga-Lill Martensson
Summary: A recent study revealed that CD38 is a novel member of the IgM-BCR coreceptor, associating with CD19 in resting B cells and with CD19 and IgM after BCR stimulation. Targeting CD38 with an antibody impairs B cell proliferation and survival, as well as the formation of IgM:CD19 synapses.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Meeting Abstract
Hematology
Lennart Lenk, Fotini Vogiatzi, Michela Carlet, Christian Vokuhl, Gunnar Cario, Martin Schrappe, Irmela Jeremias, Stephan Fuhrmann, Elias Hobeika, Hassan Jumaa, Ameera Alsadeq, Denis Martin Schewe
Meeting Abstract
Hematology
Ameera Alsadeq, Anila George Vadakumchery, Ali Almasri, Hend Abdelrasoul, Markus Werner, Lennart Lenk, Felix Seyfried, Klaus-Michael Debatin, Lueder-Hinrich Myer, Gunnar Cario, Martin Schrappe, Denis Martin Schewe, Hassan Jumaa