TPX2 promotes AURKA autophosphorylation

Stable Identifier
R-HSA-8853419
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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TPX2 promotes aurora kinase A (AURKA) activation via autophosphorylation of AURKA on threonine residue T288. Continuous association of TPX2 with AURKA facilitates active state conformation of AURKA and may prevent inactivation of AURKA by protein phosphatases (Bayliss et al. 2003).

Molecular dynamic simulations suggest the existence of two TPX2-dependent switches for Aurora A activation. 1) TPX2 binding to Aurora A forces lysine residue K143 of AURKA into an “open” state, which pulls ADP out of the ATP binding site in AURKA to promote kinase activation. 2) Arginine residue R180 of AURKA undergoes a “closed” movement upon TPX2 binding, thus capturing phosphorylated threonine T288 of AURKA into a buried position and locking AURKA in its active conformation. The existence of two TPX2-dependent switches in AURKA activation was further verified by the analysis of two AURKA mutants (K143A and R180A) (Xu et al. 2011).AURKA activation is enabled through phosphorylation and TPX2 binding; these two activating switches act synergistically and withough a predefined order (Dodson and Bayliss 2012).

Literature References
PubMed ID Title Journal Year
14580337 Structural basis of Aurora-A activation by TPX2 at the mitotic spindle

Bayliss, R, Sardon, T, Vernos, I, Conti, E

Mol. Cell 2003
22094468 Activation of Aurora-A kinase by protein partner binding and phosphorylation are independent and synergistic

Dodson, CA, Bayliss, R

J. Biol. Chem. 2012
21347367 Two TPX2-dependent switches control the activity of Aurora A

Xu, X, Wang, X, Xiao, Z, Li, Y, Wang, Y

PLoS ONE 2011
Participants
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Catalyst Activity
Catalyst Activity
Title
protein serine/threonine kinase activity of Centrosome:AURKA:TPX2:HMMR [cytosol]
Physical Entity
Activity
Orthologous Events
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Created