Article
Biology
Alison L. Kearney, Dougall M. Norris, Milad Ghomlaghi, Martin Kin Lok Wong, Sean J. Humphrey, Luke Carroll, Guang Yang, Kristen C. Cooke, Pengyi Yang, Thomas A. Geddes, Sungyoung Shin, Daniel J. Fazakerley, Lan K. Nguyen, David E. James, James G. Burchfield
Summary: The study reveals that Akt phosphorylates IRS1 and IRS2, engaging in a negative feedback mechanism that limits the synthesis of PIP3 and plasma membrane-associated PI3K. This phosphorylation leads to the depletion of IRS1/2 from the plasma membrane, reducing their interaction with the insulin receptor.
Review
Pharmacology & Pharmacy
Yazan Haddad, Marek Remes, Vojtech Adam, Zbynek Heger
Summary: The study utilized variations in 110 crystal structures to assemble eight distinct families highlighting the C-helix orientation in the N-lobe of the EGFR kinase domain. These families shared similar mutational profiles, ligand R-groups facing the C-helix, mutation sites, and DFG domain.
DRUG DISCOVERY TODAY
(2021)
Article
Medicine, Research & Experimental
Ruiyuan Zhang, Ganesan Senthil Kumar, Uwe Hansen, Martina Zoccheddu, Cristiano Sacchetti, Zachary J. Holmes, Megan C. Lee, Denise Beckmann, Yutao Wen, Zbigniew Mikulski, Shen Yang, Eugenio Santelli, Rebecca Page, Francesco Boin, Wolfgang Peti, Nunzio Bottini
Summary: Oxidation of PTP4A1 enhances its association with SRC and its profibrotic action, providing potential routes for developing antifibrotic agents for systemic sclerosis.
Article
Biochemistry & Molecular Biology
Mithila Sawant, Audrey Wilson, Dhivya Sridaran, Kiran Mahajan, Christopher J. O'Conor, Ian S. Hagemann, Jingqin Luo, Cody Weimholt, Tiandao Li, Juan Carlos Roa, Akhilesh Pandey, Xinyan Wu, Nupam P. Mahajan
Summary: Hormone receptor-positive, HER2-negative advanced breast cancers, which are sensitive to CDK4/6 inhibitors, often develop resistance. However, a study found that the non-receptor tyrosine kinase ACK1 is activated in breast cancer subtypes independent of hormone receptor status. Inhibition of ACK1 resulted in the suppression of cell cycle genes, leading to G2/M arrest and regression of palbociclib-resistant breast tumor growth. ACK1 inhibition also impaired the metastasis of breast cancer cells to the lung.
Article
Biochemistry & Molecular Biology
Qian Zhang, Shengduo Liu, Chen-Song Zhang, Qirou Wu, Xinyuan Yu, Ruyuan Zhou, Fansen Meng, Ailian Wang, Fei Zhang, Shasha Chen, Xiaojian Wang, Lei Li, Jun Huang, Yao-Wei Huang, Jian Zou, Jun Qin, Tingbo Liang, Xin-Hua Feng, Sheng-Cai Lin, Pinglong Xu
Summary: This study found that viral infection leads to a rapid decrease in blood glucose levels, resulting in the activation of AMPK. The activated AMPK directly phosphorylates TBK1, triggering the recruitment of IRF3 and the assembly of MAVS or STING signalosomes. However, depletion or inhibition of AMPK and increased glucose levels impair nucleic acid sensing, while enhancing the AMPK-TBK1 cascade significantly improves antiviral immunity.
Article
Cell Biology
Jeeho Kim, Young Jin Jeon, Sung-Chul Lim, Joohyun Ryu, Jung-Hee Lee, In-Youb Chang, Ho Jin You
Summary: Ephexin1 is highly expressed in patient tissues of colorectal cancer (CRC) and lung cancer (LC), and plays a critical role in promoting tumorigenesis through the Ras-mediated signaling pathway. Phosphorylated Ephexin1 at Ser16 and Ser18 (pSer16/18) may serve as an effective therapeutic target for CRC and LC as it interacts with oncogenic K-Ras to promote downstream MAPK signaling.
CELL DEATH & DISEASE
(2021)
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
Biochemistry & Molecular Biology
Chao Wu, Ting Xie, Ying Guo, Donghai Wang, Min Qiu, Ruyi Han, Guoliang Qing, Kaiwei Liang, Hudan Liu
Summary: CDK13 can phosphorylate RNA polymerase II and other protein substrates, with unclear role in tumorigenesis. The study identifies 4E-BP1 and eIF4B as novel CDK13 substrates and shows that CDK13 regulates mRNA translation and MYC oncoprotein synthesis in colorectal cancer. Inactivation of CDK13 and mTORC1 inhibition leads to decreased protein synthesis and increased tumor cell death, suggesting therapeutic potential of targeting CDK13 alone or in combination with rapamycin for cancer treatment.
Article
Biochemistry & Molecular Biology
Liangzhan Sun, Shaoyan Xi, Zhengdong Zhou, Feifei Zhang, Pengchao Hu, Yuzhu Cui, Shasha Wu, Ying Wang, Shayi Wu, Yanchen Wang, Yuyang Du, Jingyi Zheng, Hui Yang, Miao Chen, Qian Yan, Dandan Yu, Chaoran Shi, Yu Zhang, Dan Xie, Xin-Yuan Guan, Yan Li
Summary: Hyperactivation of RAS/MAPK signaling is common in hepatocellular carcinoma (HCC), and RIT1 is the most frequently altered member of the RAS family in HCC. RIT1 affects angiogenesis and cell survival through multiple pathways, and its overexpression is associated with poor prognosis. Combination therapy of sorafenib with AKT inhibitor shows promising results in treating RIT1-overexpressing HCC.
Article
Biochemistry & Molecular Biology
Lu Gong, Samuel Bates, Yujun Li, Xin Lin, Wenyi Wei, Xiaobo Zhou
Summary: Research found that SNPs within the FAM13A gene are significantly associated with chronic obstructive pulmonary disease and lung function. After treatment with cigarette smoke extract, FAM13A protein is phosphorylated at the serine 312 residue by AKT kinase and recognized by the CULLIN4A/DCAF1 E3 ligase complex, leading to its ubiquitination-mediated degradation. Additionally, AKT activation also leads to downregulation of FAM13A protein levels in mice with influenza or naphthalene-induced lung injury. Functionally, reduced FAM13A protein levels accelerate epithelial cell proliferation in murine lungs during the recovery phase after injury.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2023)
Article
Biology
Marina Cerqua, Orsola Botti, Maddalena Arigoni, Noemi Gioelli, Guido Serini, Raffaele Calogero, Carla Boccaccio, Paolo M. Comoglio, Dogus M. Altintas
Summary: MET is an oncogene that encodes a tyrosine kinase receptor for hepatocyte growth factor (HGF). When MET is mutated or amplified, it becomes a driver for cancer. The most common mutation in the MET gene affects the splicing sites of exon 14, leading to the deletion of a receptor domain. Our analysis showed that MET Delta 14 is dependent on HGF for kinase activation and has enhanced cellular protection and migration.
LIFE SCIENCE ALLIANCE
(2022)
Review
Pharmacology & Pharmacy
Jazlyn P. Borges, Katrina Mekhail, Gregory D. Fairn, Costin N. Antonescu, Benjamin E. Steinberg
Summary: Chronic pain is a major public health issue that is often resistant to conventional analgesics. Recent studies have implicated the epidermal growth factor receptor (EGFR) signaling pathway in chronic pain, suggesting potential therapeutic targets for this devastating condition.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Hiroshi Senoo, Daisuke Murata, May Wai, Kenta Arai, Wakiko Iwata, Hiromi Sesaki, Miho Iijima
Summary: AKT, a serine/threonine kinase, plays a crucial role in metabolism, cell growth, and cytoskeletal dynamics, and is activated by PDK1 and mTORC2. Research has uncovered that insulin activates mTORC2 towards AKT by forming a supercomplex KARATE with KRAS4B and RHOA GTPases, revealing a fundamental mechanism in insulin-regulated glucose homeostasis.
Article
Oncology
Chenyue Dai, Zeming Ma, Jiahui Si, Guo An, Wenlong Zhang, Shaolei Li, Yuanyuan Ma
Summary: The study demonstrated that inhibition of circ7312 can decrease osimertinib resistance by regulating the miR-764/MAPK1 axis and promoting pyroptosis and apoptosis, providing a novel target for osimertinib resistance therapy.
Article
Biochemistry & Molecular Biology
Mengnan Hu, Ruoxuan Bao, Miao Lin, Xiao-Ran Han, Ying-Jie Ai, Yun Gao, Kun-Liang Guan, Yue Xiong, Hai-Xin Yuan
Summary: In this study, a novel association between ALK and PFKFB3 was discovered, and it was demonstrated that ALK promotes PFKFB3 transcription through STAT3 to enhance cell proliferation and tumorigenesis, providing an alternative strategy for the treatment of ALK-positive tumors.
Article
Dermatology
Michael I. Chastkofsky, Wenjun Bie, Susan M. Ball-Kell, Yu-Ying He, Angela L. Tyner
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2015)
Article
Biochemistry & Molecular Biology
Priyank Patel, Benedikt Asbach, Elina Shteyn, Cindy Gomez, Alexander Coltoff, Sadia Bhuyan, Angela L. Tyner, Ralf Wagner, Stacy W. Blain
MOLECULAR AND CELLULAR BIOLOGY
(2015)
Article
Cell Biology
M. Peng, S. M. Ball-Kell, A. L. Tyner
CELL DEATH & DISEASE
(2015)
Article
Oncology
Priya S. Mathur, Jessica J. Gierut, Grace Guzman, Hui Xie, Rosa M. Xicola, Xavier Llor, Michael I. Chastkofsky, Ansu O. Perekatt, Angela L. Tyner
MOLECULAR CANCER RESEARCH
(2016)
Article
Multidisciplinary Sciences
Darren J. Wozniak, Andre Kajdacsy-Balla, Virgilia Macias, Susan Ball-Kell, Morgan L. Zenner, Wenjun Bie, Angela L. Tyner
NATURE COMMUNICATIONS
(2017)
Article
Oncology
Yu Zheng, Zebin Wang, Wenjun Bie, Patrick M. Brauer, Bethany E. Perez White, Jing Li, Veronique Nogueira, Pradip Raychaudhuri, Nissim Hay, Debra A. Tonetti, Virgilia Macias, Andre Kajdacsy-Balla, Angela L. Tyner
Review
Medicine, General & Internal
Yu Zheng, Angela L. Tyner
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
(2013)
Article
Oncology
Zebin Wang, Yu Zheng, Hyun Jung Park, Jing Li, Janai R. Carr, Yi-ju Chen, Megan M. Kiefer, Dragana Kopanja, Srilata Bagchi, Angela L. Tyner, Pradip Raychaudhuri
MOLECULAR CANCER THERAPEUTICS
(2013)
Article
Biochemistry & Molecular Biology
Y. Zheng, J. Gierut, Z. Wang, J. Miao, J. M. Asara, A. L. Tyner
Article
Oncology
Maoyu Peng, Rajyasree Emmadi, Zebin Wang, Elizabeth L. Wiley, Peter H. Gann, Seema A. Khan, Nilanjana Banerji, William McDonald, Szilard Asztalos, Thao N. D. Pham, Debra A. Tonetti, Angela L. Tyner
Article
Oncology
Darren J. Wozniak, Ben Hitchinson, Milica B. Gilic, Wenjun Bie, Vadim Gaponenko, Angela L. Tyner
MOLECULAR CANCER THERAPEUTICS
(2019)
Review
Biochemistry & Molecular Biology
Milica B. Gilic, Angela L. Tyner
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2020)
Article
Biochemistry & Molecular Biology
Wanian M. Alwanian, Katarina Vlajic, Wenjun Bie, Andre Kajdacsy-Balla, Angela L. Tyner
Summary: Expression of Protein tyrosine kinase 6 (PTK6) is upregulated in several human solid tumors, and it has oncogenic roles in prostate and breast cancer. This study reveals that PTK6 can directly phosphorylate SRC kinase to promote its activation. PTK6 and SRC share overlapping and unique functions in regulating signaling pathways. Furthermore, coexpression of PTK6 and SRC is observed in subsets of human prostate and breast cancer cells, and they colocalize in prostate cancer tissues.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Katarina Vlajic, Hannah Pennington Kluger, Wenjun Bie, Bradley J. Merrill, Larisa Nonn, Andre Kajdacsy-Balla, Angela L. Tyner
Summary: The example illustrates the role of tuft cells in prostate cancer, which are activated early in cancer development and increase in number with disease progression. Tuft cells contribute to the prostate cancer microenvironment and may promote the development of more advanced disease.
Review
Urology & Nephrology
Wanian M. Alwanian, Angela L. Tyner
AMERICAN JOURNAL OF CLINICAL AND EXPERIMENTAL UROLOGY
(2020)