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Table 2 AURKA downstream substrates

From: Targeting AURKA in Cancer: molecular mechanisms and opportunities for Cancer therapy

Substrates Phosphorylation sites Experimental methods Functional significance Ref
YBX1 T62, S102 Consensus motif, in vitro kinase assay, autoradiography Increases YBX1 protein stability, regulate EMT, CSC and chemoresistance. [17]
LDHB S162 In vitro kinase assay, MS analysis, point mutation, anti-phosphoserine Promotes glycolysis and biosynthesis; Promotes tumor growth. [45]
Merlin S518 In vitro kinase assay, specifc antibody Weakens merlin interaction with tubulin. [46]
RPS6KB1 T389 P-RPS6KB1 (T389) specifc antibody Reduces survival of KRAS-mutant gastrointestinal cancer cells [47]
CENP-A S7 In vitro kinase assay, truncation mutants, autoradiography Regulates mitosis especially kinetochore function. [48]
LKB1 S299 In vitro kinase assay, MS analysis,
point mutation, autoradiography
Impairs LKB1 interaction with and phosphorylation of AMPK. [49]
KCTD12 S243 Point mutation, IP, anti-phosphoserine Promotion of cancer cell proliferation and tumorigenesis. [26]
CHIP S273 Point mutation, in vitro kinase assay, autoradiography Promotes AR degradation via the proteasome pathway. [50]
ALDH1A1 T267, T442, T493 Consensus motif, point mutation, in vitro kinase assay, autoradiography Regulates protein stability, EMT and CSC phenotypes. [16]
Twist S123, T148,
S184
Consensus motif, point mutation, in vitro kinase assay, autoradiography Regulates protein stability, subcellular localization, EMT, the CSC phenotype and drug resistance. [15]
YAP S397 In vitro kinase assay, truncation mutants, MS, consensus motif Enhances transforming ability. [51]
TACC3 S558 MS, point mutation, in vitro kinase assay, autoradiography Regulates TACC3 localization to centrosomes and proximal mitotic spindles. [52]
HDM2 S166 In vitro kinase assay, specifc antibody NA [53]
β-catenin S552,
S675
In vitro kinase assay, truncation mutants, autoradiography Increases its stability and transcriptional activity [54]
ERα S167,
S305
In vitro kinase assay, truncation mutants, autoradiography Leading to increase in ERα DNA-binding and transcriptional activity. [55]
BimEL S93/94/98 Consensus motif, in vitro kinase assay, specifc antibody NA [56]
GSK-3β S9 In vitro kinase assay, specifc antibody Leading to accumulation and activation of the β-catenin/TCF complex. [57]
PLK1 T210 In vitro kinase assay, specifc antibody Centrosomal organization. [58]
IκBα S32, S36 Specifc antibody NFκB activation. [59]
VHL S72 In vitro kinase assay, MS, autoradiography NA [60]
PHLDA1 S98 In vitro kinase assay, consensus motif, autoradiography Negatively regulates PHLDA1 by promoting PHLDA1 degradation. [40]
Histone H3 S10 In vitro kinase assay, autoradiography Involved in the initiation of mitosis. [61]
YY1 S365 In vitro kinase assay, truncation mutants, consensus motif, autoradiography Abolishes its DNA binding activity and transcriptional activity. [62]
SDCBP S131,
T200
In vitro kinase assay, consensus motif, autoradiography, anti-phospho-serine/threonine Stabilizes SDCBP protein and regulates its oncogenic function. [63]
SOX2 S220, S251 In vitro kinase assay, MS Maintains the ratio of stem-cell like cells. [64]
CPAP S467 In vitro kinase assay, truncation mutants, MS, autoradiography Is required for the integrity of the spindle pole during mitosis. [65]
RalA S194 In vitro kinase assay, consensus motif, autoradiography Enhances cell migration and anchorage-independent growth. [66]
CDC25B S353 MS, in vitro kinase assay, specifc antibody Control of the onset of mitosis. [67]
NDEL1 S251 MS, in vitro kinase assay, autoradiography Centrosomal maturation, separation, and TACC3 recruitment. [68]
ASAP S625 MS, in vitro kinase assay, autoradiography Bipolar spindle assembly. [69]
MBD3 S24 In vitro kinase assay, autoradiography, consensus motif NA [70]
RASSF1A T202, S203 Consensus motif, in vitro kinase assay, autoradiography Induces M-phase cell cycle arrest. [71]
P53 S215,
S315
S106
Consensus motif, in vitro kinase assay, autoradiography S215: Abrogates DNA binding and transactivation activity;
S315: Inactivates p53 by enhancing its proteolytic degradation.
S106: Inhibit the interaction of p53 with MDM2 and prolong the half-life of p53.
[72] [73]
[74]
HURP S627, S725,
S757, S830
In vitro kinase assay,autoradiography, MS Regulates HURP stability and exhibits serum-independent growth. [75]
PP1 NA In vitro kinase assay,autoradiography Inhibits PP1 activity at mitosis. [43]
P73 S235 Consensus motif, in vitro kinase assay, autoradiography Abrogates its transactivation function; Regulates subcellular localization. [76]
TPX2 S121,
S125
Consensus motif, in vitro kinase assay, autoradiography Maintains metaphase spindle length by regulating the microtubules flux. [77]
Lats2 S83 In vitro kinase assay, truncation mutants, autoradiography Regulates centrosomal localization. [78]
LIMK2 S283, T494,
T505
Consensus motif, in vitro kinase assay, autoradiography Inhibits LIMK2 degradation and increases LIMK2 kinase activity. [14]
  1. Y-box binding protein-1 (YBX1); Lactate dehydrogenase B (LDHB); Ribosomal protein S6 kinase B1 (RPS6KB1); Centromeric protein A (CENP-A); Liver kinase B1 (LKB1); Potassium channel tetramerization domain containing 12 (KCTD12); C-terminus of HSP70-interacting protein (CHIP); Aldehyde dehydrogenase 1 (ALDH1A1); Yes-associated protein (YAP); Glycogen synthase kinase 3 beta (GSK-3β);Polo-like kinase-1 (PLK1); Pleckstrin homology-like domain family A member 1(PHLDA1); Yin Yang 1 (YY1); Syndecan binding protein (SDCBP); Sex-determining region Y (SRY)-Box 2 (SOX2); Centrosomal P4.1-associated protein (CPAP); Ral small GTPase (RalA); Neurodevelopment protein 1-like 1 (NDEL1); ASter-Associated Protein (ASAP); RAS-association domain family 1, isoform A (RASSF1A); Hepatoma upregulated protein (HURP); Protein Phosphatase 1 (PP1); Large tumor suppressor 2 (Lats2); LIM-domain kinase-2 (LIMK2); Mass spectrometry (MS); NA: not available