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
Citations
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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
Dimerization of the Pragmin Pseudo-Kinase Regulates Protein Tyrosine Phosphorylation
Céline Lecointre,Valérie Simon,Clément Kerneur,Frédéric Allemand,Aurélie Fournet,Ingrid Montarras,Jean-Luc Pons,Muriel Gelin,Constance Brignatz,Serge Urbach,Gilles Labesse,Serge Roche +11 more
TL;DR: The crystal structure of the Pragmin 906-1,368 amino acid C terminus is presented, which encompasses its kinase domain, and a dimerization mechanism by which a pseudo-kinase can induce protein tyrosine phosphorylation is revealed.
Journal ArticleDOI
STK40 Is a Pseudokinase that Binds the E3 Ubiquitin Ligase COP1.
Izabela Durzynska,Xiang Xu,Guillaume Adelmant,Scott B. Ficarro,Jarrod A. Marto,Piotrek Sliz,Sacha N. Uljon,Sacha N. Uljon,Stephen C. Blacklow,Stephen C. Blacklow +9 more
TL;DR: It is shown that STK40 interacts with Constitutive Photomorphogenic Protein 1 (COP1), relying primarily on a C-terminal sequence analogous to the motif found in Tribbles proteins, suggesting functional parallels between STK 40 and Tribbles-family proteins as COP1 adaptors.
Journal ArticleDOI
Structure of SgK223 pseudokinase reveals novel mechanisms of homotypic and heterotypic association
Onisha Patel,Onisha Patel,Michael D. W. Griffin,Santosh Panjikar,Santosh Panjikar,Weiwen Dai,Weiwen Dai,Xiuquan Ma,Howard Chan,Celine Zheng,Celine Zheng,Ashleigh Kropp,Ashleigh Kropp,James M. Murphy,James M. Murphy,Roger J. Daly,Isabelle S Lucet,Isabelle S Lucet +17 more
TL;DR: This study highlights the diversity in how the kinase fold mediates non-catalytic functions and provides mechanistic insights into how the assembly of these two oncogenic scaffolds is achieved in order to regulate signalling output.
Journal ArticleDOI
Structure of protein O-mannose kinase reveals a unique active site architecture
Qinyu Zhu,David Venzke,Ameya S Walimbe,Mary E. Anderson,Qiuyu Fu,Lisa N. Kinch,Wei Wang,Xing Chen,Nick V. Grishin,Niu Huang,Liping Yu,Jack E. Dixon,Kevin P. Campbell,Junyu Xiao +13 more
TL;DR: The crystal structure of Danio rerio POMK in complex with Mg2+ ions, ADP, aluminum fluoride, and the GalNAc-β3-GlcNAC-β4-Man trisaccharide substrate is presented, thereby providing a snapshot of the catalytic transition state of this unusual kinase.
Journal ArticleDOI
The intrinsic structure of poly(A) RNA determines the specificity of Pan2 and Caf1 deadenylases
TL;DR: Using a fully reconstituted biochemical system, it is shown that disruption of this structure—for example, by incorporation of guanosine into poly(A)—inhibits deadenylation by both Pan2 and Caf1, establishing a paradigm for specific recognition of the conformation ofpoly(A) RNA by proteins that regulate gene expression.
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