Review
Biochemistry & Molecular Biology
Zhaozhao Wang, Shu Qu, Jiahao Yuan, Wen Tian, Jinglei Xu, Rui Tao, Shilong Sun, Tao Lu, Weifang Tang, Yong Zhu
Summary: This article reviews the biological function of spleen tyrosine kinase (SYK), its relationship with diseases, and therapies targeting SYK. It also proposes the development of new therapeutic approaches for targeting SYK using new technologies.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Indira Singaram, Ashutosh Sharma, Shashank Pant, Muyun Lihan, Mi-Jeong Park, Melissa Pergande, Pawanthi Buwaneka, Yusi Hu, Nadim Mahmud, You-Me Kim, Stephanie Cologna, Vladimir Gevorgyan, Irum Khan, Emad Tajkhorshid, Wonhwa Cho
Summary: Membrane lipids control the cellular activity of kinases containing the SH2 domain. In this study, new nonlipidic small molecule inhibitors of the lipid-SH2 domain interaction were developed to block the cellular activity of their host proteins. The research shows that targeting lipid-protein interaction is a powerful approach to developing new small molecule drugs.
NATURE CHEMICAL BIOLOGY
(2023)
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
Immunology
Eszter Kaposztas, Lili Balogh, Attila Mocsai, Eva Kemecsei, Zoltan Jakus, Tamas Nemeth
Summary: Autoimmune arthritis, such as rheumatoid arthritis, affects a significant portion of the population and current therapies often fail to provide complete relief. Research suggests that inhibiting Syk tyrosine kinase can effectively reduce joint inflammation, mainly by targeting neutrophil functions.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Hannah Ennerfelt, Elizabeth L. Frost, Daniel A. Shapiro, Coco Holliday, Kristine E. Zengeler, Gabrielle Voithofer, Ashley C. Bolte, Catherine R. Lammert, Joshua A. Kulas, Tyler K. Ulland, John R. Lukens
Summary: Recent studies have highlighted the critical roles of microglia and their receptors in controlling neurotoxic material in neurodegenerative diseases. SYK plays an important role in neuroprotective functions of microglia, with its deletion exacerbating AD deposition and neuropathology. In addition, SYK regulates microglial phagocytosis and DAM acquisition in demyelinating disease.
Article
Cell Biology
Hui Yang, Wei Sun, Yan-nan Fan, Shu-yi Li, Ji-qiao Yuan, Zi-qian Zhang, Xu-yu Li, Ming-bao Lin, Qi Hou
Summary: Perilla leaf extract (PLE) exhibits anti-allergic asthma effects by attenuating airway inflammation and might partly mediate through inhibiting the Syk pathway.
MEDIATORS OF INFLAMMATION
(2021)
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
Teresa Sadras, Mickael Martin, Kohei Kume, Mark E. Robinson, Supraja Saravanakumar, Gal Lenz, Zhengshan Chen, Joo Y. Song, Tanya Siddiqi, Laura Oksa, Anne Marie Knapp, Jevon Cutler, Kadriye Nehir Cosgun, Lars Klemm, Veronika Ecker, Janet Winchester, Dana Ghergus, Pauline Soulas-Sprauel, Friedemann Kiefer, Nora Heisterkamp, Akhilesh Pandey, Vu Ngo, Lili Wang, Hassan Jumaa, Maike Buchner, Jurgen Ruland, Wing-Chung Chan, Eric Meffre, Thierry Martin, Markus Muschen
Summary: Although SYK and ZAP70 kinases share high sequence homology and serve analogous functions, their expression in B and T cells is strictly segregated throughout evolution. Aberrant ZAP70 expression is identified as a common feature in various B cell malignancies. The strict segregation of the two kinases is crucial for normal B cell selection and acts as a central safeguard against autoimmune diseases and B cell malignancies.
Article
Biochemistry & Molecular Biology
Helen T. Hobbs, Neel H. Shah, Sophie R. Shoemaker, Jeanine F. Amacher, Susan Marqusee, John Kuriyan
Summary: Using ancestral sequence reconstruction and deep mutational scanning, we have generated high-yield Syk-family kinase variants that can be expressed in bacteria. We have also developed a novel two-hybrid assay for screening and studying the function of this kinase.
Article
Pharmacology & Pharmacy
Li Li, Xulin Xu, Keyu Lv, Guijuan Zheng, Hao Wang, Shuai Chen, Lang Huang, Yi Liu, Yadong Zhang, Zhaoming Tang, Lili Zhang, Jinyu Wang, Jianlin Qiao, Hongliang Li, Xuanbin Wang, Guangmin Yao, Chao Fang
Summary: Asebogenin exhibits potent antithrombotic effects by inhibiting platelet activation and neutrophil extracellular trap formation, and its mechanism of action is mediated by targeting Syk.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Cell Biology
Gonghua Qi, Hanlin Ma, Yingwei Li, Jiali Peng, Jingying Chen, Beihua Kong
Summary: This study reveals the important role of TTK in high-grade serous ovarian cancer (HGSOC) and suggests that TTK inhibitors in combination with cisplatin may lead to improved therapeutic responses in patients with HGSOC presenting high TTK expression.
CELL DEATH & DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Tufail Ali, Farah Anjum, Arunabh Choudhury, Alaa Shafie, Amal Adnan Ashour, Abdulraheem Almalki, Taj Mohammad, Md. Imtaiyaz Hassan
Summary: Spleen tyrosine kinase (SYK) is a non-receptor tyrosine kinase that plays a crucial role in signal transduction in different cell types. In this study, two natural compounds, Isolysergic acid and Michelanugine, were identified as potential SYK inhibitors with strong affinity and specificity for the SYK binding pocket. These compounds have the potential to be developed into promising SYK inhibitors for the treatment of autoimmune disorders, cancer, and inflammatory diseases.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Medicinal
Christian Borgo, Luca Cesaro, Tsuyoshi Hirota, Keiko Kuwata, Claudio D'Amore, Thomas Ruppert, Renata Blatnik, Mauro Salvi, Lorenzo A. Pinna
Summary: CK2, a protein kinase with pleiotropic functions, is implicated in global human pathologies, particularly cancer. Selective inhibitors like CX4945 and GO289 show promise in controlling the CK2-dependent phosphoproteome.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Ilma Shakeel, Shama Khan, Sonam Roy, Fakhir Sherwani, Sheikh F. Ahmad, Sukhwinder Singh Sohal, Mohammad Afzal, Md Imtaiyaz Hassan
Summary: The signaling of SphK1 and S1P regulates various diseases, and this study explores the inhibitory potential and binding affinity of SphK1 with CA, SA, and MF. The compounds bind to SphK1 with high affinity and inhibit its kinase activity. These findings suggest the potential of designing novel anti-cancer therapeutics by targeting SphK1.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Oncology
Deepak Rohila, In Hwan Park, Timothy Pham, Jonathan Weitz, Tatiana Hurtado de Mendoza, Suresh Madheswaran, Mehreen Ishfaq, Cooper Beaman, Elisabette Tapia, Siming Sun, Jay Patel, Pablo Tamayo, Andrew M. Lowy, Shweta Joshi
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with limited treatment options. This study demonstrates that targeting macrophage spleen tyrosine kinase (Syk) can reprogram protumorigenic macrophages to an immunostimulatory phenotype, enhance CD8+ T-cell responses, and improve gemcitabine efficacy in PDAC.