There's more to death than life: Noncatalytic functions in kinase and pseudokinase signaling.
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A review of the non-catalytic functions of protein kinases can be found in this paper, where the authors consider pseudokinases, proteins that are devoid of enzymatic activity altogether and demonstrate that, beyond conventional notions of kinase function, catalytic activity can be dispensable for biological function.About:
This article is published in Journal of Biological Chemistry.The article was published on 2021-01-01 and is currently open access. It has received 40 citations till now. The article focuses on the topics: Kinase activity & Protein kinase A.read more
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Journal ArticleDOI
The intracellular domains of the EphB6 and EphA10 receptor tyrosine pseudokinases function as dynamic signalling hubs.
Lung-Yu Liang,Lung-Yu Liang,M.J. Roy,M.J. Roy,Christopher R Horne,Christopher R Horne,Jarrod J. Sandow,Jarrod J. Sandow,Minglyanna Surudoi,Laura F. Dagley,Laura F. Dagley,Samuel N. Young,Toby A. Dite,Toby A. Dite,Jeffrey J. Babon,Jeffrey J. Babon,Peter W. Janes,Onisha Patel,Onisha Patel,James M. Murphy,James M. Murphy,Isabelle S Lucet,Isabelle S Lucet +22 more
TL;DR: In this article, the authors characterized the biochemical properties and topology of EphB6 and EphA10 intracellular regions comprising the juxtamembrane (JM) region, pseudokinase and SAM domains.
Book ChapterDOI
Co-expression of recombinant RIPK3:MLKL complexes using the baculovirus-insect cell system.
TL;DR: In this paper , the authors describe methods for co-expression of pseudokinases and their interactors in insect cells, as exemplified by the MLKL pseudokinase, which is the terminal effector in the necroptosis cell death pathway, and its upstream regulator kinase RIPK3.
Journal ArticleDOI
Recent advances in targeting protein kinases and pseudokinases in cancer biology
Kristina Riegel,Parthiban Vijayarangakannan,Petros Kechagioglou,Katarzyna Bogucka,Krishnaraj Rajalingam +4 more
TL;DR: Recent developments in targeting kinases and pseudokinases are summarized and approaches on how to effectively target in cancer are discussed.
Book ChapterDOI
Dynamics of protein kinases and pseudokinases by HDX-MS.
TL;DR: In this paper , a detailed protocol for collecting an HDX-MS dataset to study the impacts of small molecule binding to a pseudokinase domain is presented, along with a discussion of the methods that have provided insights into protein kinase dynamics and how they are used to answer questions in the kinase/pseudokinase field.
Journal ArticleDOI
Redefining pseudokinases: A look at the untapped enzymatic potential of pseudokinases
TL;DR: In this paper , the authors discuss the recently characterized pseudokinases Selenoprotein O, Legionella effector SidJ, and SARS-CoV2 protein nsp12 which catalyze AMPylation, glutamylation and RNAylation.
References
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Journal ArticleDOI
The Protein Kinase Complement of the Human Genome
TL;DR: The protein kinase complement of the human genome is catalogued using public and proprietary genomic, complementary DNA, and expressed sequence tag sequences to provide a starting point for comprehensive analysis of protein phosphorylation in normal and disease states and a detailed view of the current state of human genome analysis through a focus on one large gene family.
Journal ArticleDOI
The protein kinase family: conserved features and deduced phylogeny of the catalytic domains.
TL;DR: Phylogenetic mapping of the conserved protein kinase catalytic domains can serve as a useful first step in the functional characterization of these newly identified family members.
Journal ArticleDOI
A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera
Chloé James,Valérie Ugo,Jean-Pierre Le Couedic,Judith Staerk,François Delhommeau,Catherine Lacout,Loïc Garçon,Hana Raslova,Roland Berger,Annelise Bennaceur-Griscelli,Jean-Luc Villeval,Stefan N. Constantinescu,Nicole Casadevall,William Vainchenker +13 more
TL;DR: A clonal and recurrent mutation in the JH2 pseudo-kinase domain of the Janus kinase 2 (JAK2) gene in most (> 80%) polycythaemia vera patients leads to constitutive tyrosine phosphorylation activity that promotes cytokine hypersensitivity and induces erythrocytosis in a mouse model.
Journal ArticleDOI
RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth
Georgia Hatzivassiliou,Kyung Song,Ivana Yen,Barbara J. Brandhuber,Daniel Anderson,Ryan Alvarado,Mary J. C. Ludlam,David Stokoe,Susan L. Gloor,Guy Vigers,Tony Morales,Ignacio Aliagas,Bonnie Liu,Steve Sideris,Klaus P. Hoeflich,Bijay S. Jaiswal,Somasekar Seshagiri,Hartmut Koeppen,Marcia Belvin,Lori Friedman,Shiva Malek +20 more
TL;DR: It is demonstrated that ATP-competitive kinase inhibitors can have opposing functions as inhibitors or activators of signalling pathways, depending on the cellular context, which provides new insights into the therapeutic use of ATP- competitive RAF inhibitors.
Journal ArticleDOI
The Pseudokinase MLKL Mediates Necroptosis via a Molecular Switch Mechanism
James M. Murphy,Peter E. Czabotar,Peter E. Czabotar,Joanne M Hildebrand,Joanne M Hildebrand,Isabelle S Lucet,Jian-Guo Zhang,Jian-Guo Zhang,Silvia Alvarez-Diaz,Silvia Alvarez-Diaz,Rowena S. Lewis,Rowena S. Lewis,Najoua Lalaoui,Najoua Lalaoui,Donald Metcalf,Donald Metcalf,Andrew I. Webb,Andrew I. Webb,Samuel N. Young,Samuel N. Young,Leila N. Varghese,Leila N. Varghese,Gillian M. Tannahill,Gillian M. Tannahill,Esme C. Hatchell,Esme C. Hatchell,Ian J. Majewski,Ian J. Majewski,Toru Okamoto,Toru Okamoto,Renwick C. J. Dobson,Renwick C. J. Dobson,Douglas J. Hilton,Douglas J. Hilton,Jeffrey J. Babon,Jeffrey J. Babon,Nicos A. Nicola,Nicos A. Nicola,Andreas Strasser,Andreas Strasser,John Silke,John Silke,Warren S. Alexander,Warren S. Alexander +43 more
TL;DR: Structural-guided mutation of the MLKL pseudoactive site resulted in constitutive, RIPK3-independent necroptosis, demonstrating that modification ofMLKL is essential for propagation of the ne croptosis pathway downstream of RIPK 3.
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