| Interacting proteins: Q9ULW0 and O14965 |
Pubmed |
SVM Score :0.89766914 |
| TPX 2 was identified by mass spectrometry as a major protein coimmunoprecipitating specifically with Aurora A from mitotic HeLa cell extracts . 0.89766914^^^ |
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| Interacting proteins: Q9ULW0 and O14965 |
Pubmed |
SVM Score :0.51147681 |
| We have uncovered the molecular mechanism of Aurora A activation by determining crystal structures of its phosphorylated form both with and without a 43 residue long domain of TPX 2 that we identified as fully functional for kinase activation and protection from dephosphorylation . 0.51147681^^^ |
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| Interacting proteins: Q9ULW0 and O14965 |
Pubmed |
SVM Score :0.55914094 |
| Despite the near identity of amino acid sequence in the catalytic domain , monomeric Aurora B is 50 fold lower in activity than monomeric Aurora A , and previous studies have shown that TPX 2 binding to the catalytic domain activates Aurora A but not Aurora B . 0.55914094^^^ |
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| Interacting proteins: Q9ULW0 and O14965 |
Pubmed |
SVM Score :0.0 |
| Ran modulates spindle assembly by regulating a subset of TPX 2 and Kid activities including Aurora A activation . ^^^ In the amino terminal domain of TPX 2 we identified nuclear targeting information , microtubule binding and Aurora A binding activities . ^^^ Nuclear transport receptor binding to TPX 2 inhibited Aurora A binding activity but not the microtubule binding activity of TPX 2 . ^^^ Inhibition of the interaction between TPX 2 and Aurora A prevented Aurora A activation and recruitment to microtubules . ^^^ |
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| Interacting proteins: Q9ULW0 and O14965 |
Pubmed |
SVM Score :0.0 |
| Regulation of Xenopus Aurora A activation by TPX 2 . ^^^ One such protein is TPX 2 , a required spindle assembly factor in higher eukaryotes whose ability to activate Aurora A by direct binding to the kinase catalytic domain has been established by biochemical and structural analysis . ^^^ Association of Aurora A with TPX 2 leads to activation of the kinase , in parallel with phosphorylation of TPX 2 . ^^^ We identify the sites as three Ser residues in the N terminus of TPX 2 ; however , mutation of these residues does not affect Aurora A activation by TPX 2 . ^^^ In contrast , the mutation of a putative Aurora A binding motif in TPX 2 abolishes both phosphorylation of TPX 2 and activation of Aurora A . ^^^ |
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| Interacting proteins: Q9ULW0 and O14965 |
Pubmed |
SVM Score :0.0 |
| We report here that Ran GTP stimulates the interaction between TPX 2 and the Xenopus Aurora A kinase , Eg 2 . ^^^ As the phosphorylation of Eg 2 stimulated by the Ran GTP TPX 2 pathway is essential for spindle assembly , we hypothesize that the Ran GTP gradient established by the condensed chromosomes is translated into the Aurora A kinase gradient on the microtubules to regulate spindle assembly and dynamics . . ^^^ |
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| Interacting proteins: Q9ULW0 and O14965 |
Pubmed |
SVM Score :0.0 |
| Aurora A localization to the mitotic spindle depends on the motor binding protein TPX 2 ( Targeting Protein for Xenopus kinesin like protein 2 ) , but the protein ( s ) involved in Aurora A activation are unknown [ 11 13 ] . ^^^ Here , we purify an activator of Aurora A from Xenopus eggs and identify it as TPX 2 . ^^^ Remarkably , Aurora A that has been fully deactivated by Protein Phosphatase 2A ( PP2A ) becomes phosphorylated and reactivated by recombinant TPX 2 in an ATP dependent manner . ^^^ Increased phosphorylation and activation of Aurora A requires its own kinase activity , suggesting that TPX 2 stimulates autophosphorylation and autoactivation of the enzyme . ^^^ Consistently , wild type Aurora A , but not a kinase inactive mutant , becomes autophosphorylated on the regulatory T loop residue ( Thr 295 ) after TPX 2 treatment . ^^^ |
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| Interacting proteins: Q9ULW0 and O14965 |
Pubmed |
SVM Score :0.0 |
| An exciting study in this issue reveals how binding of the microtubule associated protein TPX 2 to the mitotic kinase Aurora A induces a conformational change . ^^^ |
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| Interacting proteins: Q9ULW0 and O14965 |
Pubmed |
SVM Score :0.0 |
| By profiling of gene expressions associated with downregulation of MAPK 1 induced by exogenous overexpression of DUSP 6 in pancreatic cancer cells , we found that AURKA / STK15 , the gene encoding Aurora A kinase , which plays key roles in cellular mitosis , was among the downregulated genes along with its related genes , which included AURKB , TPX 2 and CENPA . ^^^ |
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| Interacting proteins: Q9ULW0 and O14965 |
Pubmed |
SVM Score :0.0 |
| Determinants for Aurora A activation and Aurora B discrimination by TPX 2 . ^^^ Surprisingly , our recent structural studies indicate that TPX 2 regulates Aurora A activity by binding at a site that is conserved almost completely on Aurora B . ^^^ Here we investigate molecular determinants of TPX 2 Aurora A recognition . ^^^ Using structure based mutagenesis , we show that a single amino acid difference on the surface of the kinase catalytic domain is key to the precision with which TPX 2 discriminates between Aurora A and Aurora B . ^^^ |
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| Interacting proteins: Q9ULW0 and O14965 |
Pubmed |
SVM Score :0.0 |
| TPX 2 has multiple functions during mitosis , including microtubule nucleation around the chromosomes and the targeting of Xklp 2 and Aurora A to the spindle . ^^^ We have performed a detailed domain functional analysis of TPX 2 and found that a large N terminal domain containing the Aurora A binding peptide interacts directly with and nucleates microtubules in pure tubulin solutions . ^^^ By contrast , a large C terminal domain of TPX 2 that does not bind directly to pure microtubules and does not bind Aurora A kinase rescues microtubule nucleation in response to RanGTP and spindle assembly in TPX 2 depleted extract . ^^^ |
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| Interacting proteins: Q9ULW0 and O14965 |
Pubmed |
SVM Score :0.0 |
| The structure of the complex of Aurora A with the TPX 2 activator has been reported previously . ^^^ The Aurora B : INCENP complex is remarkably different from the Aurora A : TPX 2 complex . ^^^ |
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| Interacting proteins: Q9ULW0 and O14965 |
Pubmed |
SVM Score :0.0 |
| Aurora A substrate activators include TPX 2 and Ajuba , whereas the only known Aurora B substrate activator is the chromosomal passenger INCENP . ^^^ |
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| Interacting proteins: Q9ULW0 and O14965 |
Pubmed |
SVM Score :0.0 |
| An essential function of the C . elegans ortholog of TPX 2 is to localize activated aurora A kinase to mitotic spindles . ^^^ TPX 2 is also known to bind to and activate Aurora A kinase and target it to the spindle . ^^^ However , the relationship between the TPX 2 Aurora A interaction and the role of TPX 2 in spindle assembly is unclear . ^^^ Thus , activation and targeting of Aurora A appears to be an ancient and conserved function of TPX 2 that plays a central role in mitotic spindle assembly . . ^^^ |
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| Interacting proteins: Q9ULW0 and O14965 |
Pubmed |
SVM Score :0.0 |
| An Aurora A regulatory module has been identified in two different proteins : TPX 2 in Xenopus laevis and TPXL 1 in C . elegans . ^^^ |
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| Interacting proteins: Q9ULW0 and O14965 |
Pubmed |
SVM Score :0.0 |
| Here , we report the development of functional assays that allow us to show that activation of AurA by TPX 2 is essential for Ran stimulated spindle assembly in the presence or absence of centrosomes . ^^^ |
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| Interacting proteins: Q9ULW0 and O14965 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q9ULW0 and O14965 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q9ULW0 and O14965 |
Pubmed |
SVM Score :0.0 |
| NA |
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