Article
Cell Biology
Louise Thines, Zhigang Li, David B. Sacks
Summary: This study reveals a novel mechanism by which MET-catalyzed phosphorylation of IQGAP1 regulates its interaction with SH2-containing proteins, providing new insights into how IQGAP1 coordinates intracellular signaling.
Article
Biochemistry & Molecular Biology
Zi Wang, Yubao Shan, Ru Wang, Heng Zhou, Rui Hu, Ying Li, Jiang Zhu, Yunhuang Yang, Maili Liu
Summary: This study investigated the interaction between SHIP2-SH2 and CagA protein from a structural perspective using NMR spectroscopy. The results showed that EPIYA-C and -D have high affinity to the binding site of SHIP2-SH2, while EPIYA-A and -B have weak affinity. The study also revealed the selective preference of SHIP2-SH2 for aliphatic residues at the pY+3 position in its ligand. These findings provide insights into the ligand sequence and the mechanism by which CagA protein hijacks SHIP2.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Szabolcs Sipeki, Kitti Koprivanacz, Tamas Takacs, Anita Kurilla, Loretta Laszlo, Virag Vas, Laszlo Buday
Summary: Signal transduction is essential for cells to perceive and respond to information, with subcellular hubs formed via protein interactions playing a central role. The SH2 and SH3 domains serve as prototypes for interaction domains that recognize proteins, lipids, nucleic acids, and small molecules. The lipid-binding properties of SH2 and SH3 domains are also important for modulating complex assembly.
Article
Chemistry, Analytical
Qiwen Peng, Min Zhang, Guoyue Shi
Summary: Exploring the upstream and downstream relationship of Aβ in Alzheimer's disease (AD) is of great significance. In this study, a peptide-functionalized EG-FET sensor was developed to monitor c-Abl level with high sensitivity and selectivity. The sensor was successfully used to quantify c-Abl activity in AD transgenic mice and explore the interaction between c-Abl and Aβ.
ANALYTICAL CHEMISTRY
(2022)
Article
Cell Biology
Briana C. Bywaters, Gonzalo M. Rivera
Summary: The non-catalytic region of tyrosine kinase (Nck) family of adaptors, consisting of Nck1 and Nck2, plays a key role in cellular information flow and specificity by recruiting components of signaling networks. Nck adaptors are involved in cytoskeletal remodeling, immune cell receptor activation, cell adhesion, and have some functional redundancy between Nck1 and Nck2.
JOURNAL OF CELL SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Justin Lawrie, Sean Waldrop, Anya Morozov, Wei Niu, Jiantao Guo
Summary: Protein tyrosine O-sulfation is crucial for various biological processes, but sulfated tyrosine residues are challenging to detect due to their instability and low abundance. This study engineered SH2 mutants as an antisulfotyrosine antibody mimic, demonstrating high affinity and specificity to sulfotyrosine through tailored selection schemes. Molecular docking simulations supported the characteristics of these SH2 mutants, enhancing the detection and enrichment of sulfoproteins.
ACS CHEMICAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Livia Pagano, Valeria Pennacchietti, Awa Diop, Daniele Santorelli, Paola Pietrangeli, Lucia Marcocci, Caterina Nardella, Francesca Malagrino, Angelo Toto, Stefano Gianni
Summary: In this study, the folding properties of the multidomain protein Grb2 were analyzed, revealing the interaction between the SH2 and C-SH3 domains during folding. These findings contribute to a better understanding of multidomain protein folding.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2022)
Article
Cell Biology
Xu Liu, Yao-Jie Pan, Meng-Jie Kang, Xin Jiang, Zhong-Ying Guo, Dong-Sheng Pei
Summary: In this study, it was found that P21-activated kinase 5 (PAK5) is overexpressed in renal cell carcinoma (RCC) and promotes metastasis by enhancing epithelial-mesenchymal transition. PAK5 binds to Slug and phosphorylates it, leading to the activation of N-cadherin. Therefore, phosphorylated Slug-S87 could serve as a therapeutic target for progressive RCC.
CELLULAR SIGNALLING
(2023)
Article
Immunology
Huynh Dinh Chien, Antonella Pantaleo, Kristina R. Kesely, Panae Noomuna, Karson S. Putt, Tran Anh Tuan, Philip S. Low, Francesco M. Turrini
Summary: The coadministration of imatinib with standard of care (SOC) in uncomplicated P. falciparum malaria patients led to a faster decline in parasite density and fever, without any delayed parasite clearance. The improvements were most significant in patients with the highest parasite density, where serious complications and death are most common.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Multidisciplinary Sciences
Alicia E. Woock, Jacqueline M. Grible, Amy L. Olex, J. Chuck Harrell, Patricija Zot, Michael Idowu, Charles V. Clevenger
Summary: This study investigates the phosphorylation of STAT5a at serine residues S726, S780, and tyrosine residue Y694 in MCF7 luminal breast cancer cells in response to prolactin, and how these phosphorylation events impact gene expression and functional pathways related to breast cancer. The research shows that mutations at different phospho-sites on STAT5a have distinct effects on clonogenicity and proliferation in breast cancer cells, providing novel insights into the role of STAT5a in breast cancer pathogenesis.
SCIENTIFIC REPORTS
(2021)
Article
Hematology
Lauren M. Brown, Soroor Hediyeh-Zadeh, Teresa Sadras, Hannah Huckstep, Jarrod J. Sandow, Ray C. Bartolo, Hansen J. Kosasih, Nadia M. Davidson, Breon Schmidt, Stefan Bjelosevic, Ricky Johnstone, Andrew Webb, Seong L. Khaw, Alicia Oshlack, Melissa J. Davis, Paul G. Ekert
Summary: This study identified a rare SFPQ-ABL1 fusion gene that plays a crucial role in cellular transformation in Ph-like ALL. Unlike other ABL1 fusion genes, SFPQ-ABL1 exhibits differences in subcellular localization, proliferative capacity, and activation of cellular pathways. These findings highlight the significance of fusion partners in mediating the function of ABL1 fusion genes.
Article
Cell Biology
Qian Xue, Sophia R. S. Varady, Trinity Q. Alaka'i Waddell, Mackenzie R. Roman, James Carrington, Minna Roh-Johnson
Summary: This study reveals the dynamic regulation of focal adhesions in cell migration in the native environment using a zebrafish model and a mouse model. The researchers found that the phosphorylation of Y118-Paxillin, a key site of phosphoregulation, is reduced in migrating cells in vivo compared to in vitro. Furthermore, expression of a non-phosphorylatable version of Y118-Paxillin promotes focal adhesion disassembly and cell migration in vivo. The findings also suggest that the CRKII-DOCK180/RacGEF pathway is activated in cells expressing non-phosphorylatable Y118-Paxillin.
JOURNAL OF CELL BIOLOGY
(2023)
Article
Oncology
Heidelinde Jaekel, Martin Taschler, Karin Jung, Christina Weinl, Fragka Pegka, Michael Keith Kullmann, Silvio Roland Podmirseg, Sayantanee Dutta, Markus Moser, Ludger Hengst
Summary: The study reveals the importance of p27 tyrosine phosphorylation in v-ABL and BCR::ABL1(p190)-induced transformation. Surprisingly, p27-Y88F mice are more susceptible to v-ABL-induced leukemia/lymphoma, possibly due to a robust reduction of p27-Y88F levels leading to enhanced cell proliferation and accelerated leukemia progression.
Article
Chemistry, Medicinal
Dhanaji M. Lade, Roxy Nicoletti, James Mersch, Yehenew M. Agazie
Summary: SHP2 is an important oncogene in cancers driven by overexpression of receptor tyrosine kinases. In this study, we developed an optimized derivative BPDA2 as an SHP2 inhibitor with increased potency and selectivity, and demonstrated its efficacy and selectivity in cellular assays.
EUROPEAN JOURNAL OF 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)
Article
Biochemical Research Methods
Karsten Krug, Philipp Mertins, Bin Zhang, Peter Hornbeck, Rajesh Raju, Rushdy Ahmad, Matthew Szucs, Filip Mund, Dominique Forestier, Judit Jane-Valbuena, Hasmik Keshishian, Michael A. Gillette, Pablo Tamayo, Jill P. Mesirov, Jacob D. Jaffe, Steven A. Carr, D. R. Mani
MOLECULAR & CELLULAR PROTEOMICS
(2019)
Article
Biochemistry & Molecular Biology
Peter V. Hornbeck, Jon M. Kornhauser, Vaughan Latham, Beth Murray, Vidhisha Nandhikonda, Alex Nord, Elzbieta Skrzypek, Travis Wheeler, Bin Zhang, Florian Gnad
NUCLEIC ACIDS RESEARCH
(2019)
Article
Genetics & Heredity
Claire M. Simpson, Bin Zhang, Peter Hornbeck, Florian Gnad
BMC MEDICAL GENOMICS
(2019)
Article
Multidisciplinary Sciences
Yajun Jiang, Paolo Rossi, Charalampos G. Kalodimos
Article
Oncology
Viralkumar Davra, Tamjeed Saleh, Ke Geng, Stanley Kimani, Dhriti Mehta, Canan Kasikara, Brendan Smith, Nicholas W. Colangelo, Bryan Ciccarelli, Hong Li, Edouard I. Azzam, Charalampos G. Kalodimos, Raymond B. Birge, Sushil Kumar
MOLECULAR CANCER RESEARCH
(2020)
News Item
Biophysics
Mary C. Clay, Charalampos G. Kalodimos
BIOPHYSICAL JOURNAL
(2020)
Article
Multidisciplinary Sciences
Tao Xie, Tamjeed Saleh, Paolo Rossi, Charalampos G. Kalodimos
Article
Biochemistry & Molecular Biology
Youlin Xia, Tairan Yuwen, Aizhuo Liu, Charalampos G. Kalodimos
Summary: NMR has the capability to offer integrated insight into both the structure and intrinsic dynamics of biomolecules, with CEST experiments allowing quantitative investigation of chemical exchange phenomena. However, using the simple CW method can lead to H-2 decoupling sidebands in the CEST experiments, affecting the detection of minor dips of excited states. By developing methods using pseudo-continuous waves for H-2 decoupling, the sidebands can be successfully removed, as validated on Bruker spectrometers at different field strengths.
JOURNAL OF BIOMOLECULAR NMR
(2021)
Article
Chemistry, Organic
Brandon M. Young, Paolo Rossi, P. Jake Slavish, Yixin Cui, Munia Sowaileh, Jitendra Das, Charalampos G. Kalodimos, Zoran Rankovic
Summary: Isotopically labeled amino acids are commonly used for studying protein structure and dynamics by NMR. This study presents a facile gram-scale synthesis of compounds 1b and 2b under standard laboratory conditions from a common intermediate. The improved signal intensity with lower amounts of labeled precursor makes 1b and 2b potential alternatives to current labeling approaches.
Article
Biochemistry & Molecular Biology
Tao Xie, Tamjeed Saleh, Paolo Rossi, Darcie Miller, Charalampos G. Kalodimos
Summary: Imatinib binds to an allosteric pocket on Abl, promoting kinase activity and providing a mechanism for drug resistance in Abl variants with imatinib-resistant mutations in the catalytic site. Combining imatinib with allosteric inhibitors maximizes their inhibitory effect on Bcr-Abl.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Biao Yuan, Athina G. Portaliou, Rinky Parakra, Jochem H. Smit, Jiri Wald, Yichen Li, Bindu Srinivasu, Maria S. Loos, Harveer Singh Dhupar, Dirk Fahrenkamp, Charalampos G. Kalodimos, Franck Duong van Hoa, Thorben Cordes, Spyridoula Karamanou, Thomas C. Marlovits, Anastassios Economou
Summary: Type III protein secretion is common in Gram-negative pathogens, with SctV forming peripheral oligomeric clusters in EPEC and serving as a key receptor for different chaperone/exported protein pairs. The dynamic motions of SctV protomers, modulated by chaperones and ATPase, may allosterically affect the secretion process.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Andrey V. Reshetnyak, Paolo Rossi, Alexander G. Myasnikov, Munia Sowaileh, Jyotidarsini Mohanty, Amanda Nourse, Darcie J. Miller, Irit Lax, Joseph Schlessinger, Charalampos G. Kalodimos
Summary: ALK is a receptor tyrosine kinase that regulates important functions in the central nervous system, and mutations in this gene may lead to neuroblastoma. Research has revealed a mechanism of RTK activation that allows dimerization by different ligands, with the complex architecture of the receptor-ligand complex playing a key role in this process.
Article
Biochemistry & Molecular Biology
Mary C. Clay, Tamjeed Saleh, Samuel Kamatham, Paolo Rossi, Charalampos G. Kalodimos
Summary: Methyl-TROSY spectroscopy has expanded the application of solution-state NMR to study supra-molecular machineries. Accurate methyl chemical shift assignment remains a challenge. This work presents the current technology for methyl labeling, data collection, data analysis, and automated methyl assignment approaches, along with Python extensions and a standalone network analysis program for the task.