Table 2.
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. |
[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] |
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