scholarly journals Ligand discrimination between active and inactive activation loop conformations of Aurora-A kinase is unmodified by phosphorylation

2019 ◽  
Vol 10 (14) ◽  
pp. 4069-4076 ◽  
Author(s):  
James A. H. Gilburt ◽  
Paul Girvan ◽  
Julian Blagg ◽  
Liming Ying ◽  
Charlotte A. Dodson
Keyword(s):  
Activation Loop ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Conformational Preference ◽  
Loop Conformations

Activation loop phosphorylation changes the position of equilibrium between DFG-in-like and DFG-out-like conformations but not the conformational preference of inhibitors.

scholarly journals Detection of Ligand‐induced Conformational Changes in the Activation Loop of Aurora‐A Kinase by PELDOR Spectroscopy

ChemistryOpen ◽  
2016 ◽  
Vol 5 (6) ◽  
pp. 531-534 ◽  
Author(s):  
Selena G. Burgess ◽  
Maria Grazia Concilio ◽  
Richard Bayliss ◽  
Alistair J. Fielding
Keyword(s):  
Conformational Changes ◽  
Activation Loop ◽  
Aurora A Kinase ◽  
Aurora A

scholarly journals Dynamic Equilibrium of the Aurora A Kinase Activation Loop Revealed by Single-Molecule Spectroscopy

2017 ◽  
Vol 56 (38) ◽  
pp. 11409-11414 ◽  
Author(s):  
James A. H. Gilburt ◽  
Hajrah Sarkar ◽  
Peter Sheldrake ◽  
Julian Blagg ◽  
Liming Ying ◽  
...  
Keyword(s):  
Single Molecule ◽  
Dynamic Equilibrium ◽  
Activation Loop ◽  
Single Molecule Spectroscopy ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Kinase Activation

scholarly journals Dynamic Equilibrium of the Aurora A Kinase Activation Loop Revealed by Single-Molecule Spectroscopy

2017 ◽  
Vol 129 (38) ◽  
pp. 11567-11572
Author(s):  
James A. H. Gilburt ◽  
Hajrah Sarkar ◽  
Peter Sheldrake ◽  
Julian Blagg ◽  
Liming Ying ◽  
...  
Keyword(s):  
Single Molecule ◽  
Dynamic Equilibrium ◽  
Activation Loop ◽  
Single Molecule Spectroscopy ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Kinase Activation

Ancient origins of allosteric activation in a Ser-Thr kinase

Science ◽  
2020 ◽  
Vol 367 (6480) ◽  
pp. 912-917 ◽  
Author(s):  
Adelajda Hadzipasic ◽  
Christopher Wilson ◽  
Vy Nguyen ◽  
Nadja Kern ◽  
Chansik Kim ◽  
...  
Keyword(s):  
Activation Mechanism ◽  
Activation Loop ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Allosteric Activation ◽  
Fundamental Interest ◽  
Evolutionary Path ◽  
Cellular Events ◽  
Sequence Reconstruction ◽  
Allosteric Activator

A myriad of cellular events are regulated by allostery; therefore, evolution of this process is of fundamental interest. Here, we use ancestral sequence reconstruction to resurrect ancestors of two colocalizing proteins, Aurora A kinase and its allosteric activator TPX2 (targeting protein for Xklp2), to experimentally characterize the evolutionary path of allosteric activation. Autophosphorylation of the activation loop is the most ancient activation mechanism; it is fully developed in the oldest kinase ancestor and has remained stable over 1 billion years of evolution. As the microtubule-associated protein TPX2 appeared, efficient kinase binding to TPX2 evolved, likely owing to increased fitness by virtue of colocalization. Subsequently, TPX2-mediated allosteric kinase regulation gradually evolved. Surprisingly, evolution of this regulation is encoded in the kinase and did not arise by a dominating mechanism of coevolution.

Centrosome Aurora A gradient ensures single polarity axis in C. elegans embryos

2020 ◽  
Vol 48 (3) ◽  
pp. 1243-1253 ◽  
Author(s):  
Sukriti Kapoor ◽  
Sachin Kotak
Keyword(s):  
Symmetry Breaking ◽  
Cell Fate ◽  
Cell Cortex ◽  
Axis Formation ◽  
Aurora A Kinase ◽  
Aurora A ◽  
C Elegans ◽  
Cell Embryo ◽  
Polarity Establishment

Cellular asymmetries are vital for generating cell fate diversity during development and in stem cells. In the newly fertilized Caenorhabditis elegans embryo, centrosomes are responsible for polarity establishment, i.e. anterior–posterior body axis formation. The signal for polarity originates from the centrosomes and is transmitted to the cell cortex, where it disassembles the actomyosin network. This event leads to symmetry breaking and the establishment of distinct domains of evolutionarily conserved PAR proteins. However, the identity of an essential component that localizes to the centrosomes and promotes symmetry breaking was unknown. Recent work has uncovered that the loss of Aurora A kinase (AIR-1 in C. elegans and hereafter referred to as Aurora A) in the one-cell embryo disrupts stereotypical actomyosin-based cortical flows that occur at the time of polarity establishment. This misregulation of actomyosin flow dynamics results in the occurrence of two polarity axes. Notably, the role of Aurora A in ensuring a single polarity axis is independent of its well-established function in centrosome maturation. The mechanism by which Aurora A directs symmetry breaking is likely through direct regulation of Rho-dependent contractility. In this mini-review, we will discuss the unconventional role of Aurora A kinase in polarity establishment in C. elegans embryos and propose a refined model of centrosome-dependent symmetry breaking.

Activation of Aurora A kinase through the FGF1/FGFR signaling axis sustains the stem cell characteristics of glioblastoma cells

2016 ◽  
Vol 344 (2) ◽  
pp. 153-166 ◽  
Author(s):  
Yi-Chao Hsu ◽  
Chien-Yu Kao ◽  
Yu-Fen Chung ◽  
Don-Ching Lee ◽  
Jen-Wei Liu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Glioblastoma Cells ◽  
Fgfr Signaling ◽  
Signaling Axis

scholarly journals MLN8054, an Inhibitor of Aurora A Kinase, Induces Senescence in Human Tumor Cells Both In vitro and In vivo

2010 ◽  
Vol 8 (3) ◽  
pp. 373-384 ◽  
Author(s):  
Jessica J. Huck ◽  
Mengkun Zhang ◽  
Alice McDonald ◽  
Doug Bowman ◽  
Kara M. Hoar ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Human Tumor ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Human Tumor Cells
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