There's more to death than life: Noncatalytic functions in kinase and pseudokinase signaling.
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TLDR
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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Targeting the Non-Catalytic Functions: a New Paradigm for Kinase Drug Discovery?
TL;DR: The characterized noncatalytic functions of kinases are summarized, and the recent progress on developing small-molecule modulators of the noncatalyst functions of Kinase catalytic functions are highlighted.
Journal ArticleDOI
Blocking Non-enzymatic Functions by PROTAC-Mediated Targeted Protein Degradation.
TL;DR: In this paper , the authors summarize and analyze recent progress in blocking non-enzymatic functions of target proteins by PROTAC-mediated degradation, highlighting representative case studies and discussing the pharmacological features originating from inhibition of the non enzymatic function.
Journal ArticleDOI
Chemical Probes for Understudied Kinases: Challenges and Opportunities.
Ricardo A. M. Serafim,Jonathan M. Elkins,William J. Zuercher,Stefan Laufer,Matthias Gehringer +4 more
TL;DR: In this paper, the authors highlight recent case studies illustrating the development of high-quality chemical probes for less-studied kinases and their application in target validation and discuss the associated challenges and opportunities.
Journal ArticleDOI
Looking lively: emerging principles of pseudokinase signaling.
Joshua B. Sheetz,Mark A. Lemmon +1 more
TL;DR: In this paper , the authors discuss recent structural data on conformational transitions and nucleotide binding by pseudokinases and discuss how biasing this conformational toggle may provide opportunities to target pseudokinase pharmacologically in disease.
Journal ArticleDOI
Structure vs. Function of TRIB1—Myeloid Neoplasms and Beyond
TL;DR: The TRIB1 family of proteins as discussed by the authors plays important roles in differentiation, development, and oncogenesis, and is known to be accessible to small-molecule inhibitors in spite of its inability to bind ATP.
References
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Journal ArticleDOI
Location, location, location: A compartmentalized view of TNF-induced necroptotic signaling.
Andre L. Samson,Andre L. Samson,Sarah E Garnish,Sarah E Garnish,Joanne M Hildebrand,Joanne M Hildebrand,James M. Murphy,James M. Murphy +7 more
TL;DR: In this article, a network of modulators surrounding the necroptotic signaling core is proposed, which tunes neproptosis in a context-, cell type-, and species-dependent manner.
Journal ArticleDOI
A Bacterial Effector Mimics a Host HSP90 Client to Undermine Immunity.
Victor Lopez,Brenden C. Park,Dominika Nowak,Anju Sreelatha,Patrycja Zembek,Jessie Fernandez,Kelly A. Servage,Marcin Gradowski,Jacek Hennig,Diana R. Tomchick,Krzysztof Pawłowski,Magdalena Krzymowska,Vincent S. Tagliabracci +12 more
TL;DR: It is demonstrated that phosphorylation of HSP90 prevents activation of immune receptors that trigger the hypersensitive response in plants, and a family of bacterial effector kinases with toxin-like properties is uncovered, revealing a previously unrecognized betrayal mechanism by which bacterial pathogens modulate host immunity.
Journal ArticleDOI
An asymmetric PAN3 dimer recruits a single PAN2 exonuclease to mediate mRNA deadenylation and decay
Stefanie Jonas,Mary Christie,Daniel Peter,Dipankar Bhandari,Belinda Loh,Eric Huntzinger,Oliver Weichenrieder,Elisa Izaurralde +7 more
TL;DR: Crystal structures are described that show that Neurospora crassa PAN2 comprises two independent structural units: a C-terminal catalytic unit and an N-Terminal assembly unit that engages in a bipartite interaction with PAN3 dimers.
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The crystal structure of pseudokinase PEAK1 (Sugen kinase 269) reveals an unusual catalytic cleft and a novel mode of kinase fold dimerization.
Byung Hak Ha,Titus J. Boggon +1 more
TL;DR: PEAK1's kinase cleft is occluded, and its newly identified SHED region may promote an unexpected dimerization mode, which may reclassify the latter as a member of the new kinase family 3 group.
Journal ArticleDOI
MyD88 Death-Domain Oligomerization Determines Myddosome Architecture: Implications for Toll-like Receptor Signaling.
Martin C. Moncrieffe,Daniel Bollschweiler,Bing Li,Pawel A. Penczek,Lee Hopkins,Clare E. Bryant,David Klenerman +6 more
TL;DR: It is shown that the death domains of human MyD88 spontaneously and reversibly associate to form helical filaments in vitro, suggesting that intracellularly, the MyD 88 scaffold may be pre-formed and poised for recruitment of IRAKs on receptor activation and TIR engagement.
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