Thr198
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Home > Phosphorylation Site Page: > Thr198  -  p27Kip1 (human)

Site Information
PGLRRRQt_______   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 448781
Associated spectra:  1 CST

In vivo Characterization
Methods used to characterize site in vivo:
immunoassay ( 10 ) , immunoprecipitation ( 10 , 14 , 16 , 17 ) , mass spectrometry ( 12 , 15 , 19 , 20 , 21 ) , mutation of modification site ( 1 , 2 , 4 , 10 , 17 , 18 , 22 , 23 , 24 , 25 , 27 ) , phospho-antibody ( 3 , 7 , 11 , 13 , 14 , 16 , 17 , 18 , 22 , 23 , 24 , 25 , 27 ) , phosphoamino acid analysis ( 22 ) , phosphopeptide mapping ( 22 ) , western blotting ( 1 , 3 , 4 , 7 , 10 , 11 , 13 , 14 , 16 , 18 , 22 , 23 , 24 )
Disease tissue studied:
bone cancer ( 1 , 22 ) , osteosarcoma ( 1 ) , brain cancer ( 10 ) , glioblastoma ( 10 ) , glioma ( 10 ) , breast cancer ( 16 , 18 , 22 , 23 ) , kidney cancer ( 13 ) , leukemia ( 17 ) , chronic myelogenous leukemia ( 17 ) , liver cancer ( 11 ) , neuroblastoma ( 14 ) , ovarian cancer ( 10 ) , prostate cancer ( 17 ) , melanoma skin cancer ( 18 , 22 ) , fibrosarcoma of soft tissue ( 10 ) , cancer, squamous cell carcinoma ( 10 ) , thyroid cancer ( 24 ) , anaplastic thyroid carcinoma ( 24 ) , follicular thyroid carcinoma ( 24 ) , papillary thyroid carcinoma ( 24 )
Relevant cell line - cell type - tissue:

Upstream Regulation
Regulatory protein:
DYRK1B (human) ( 3 ) , EGLN3 (human) ( 5 ) , LKB1 (human) ( 22 ) , MIF4GD (human) ( 4 )
Putative in vivo kinases:
Akt1 (human) ( 24 , 25 , 27 ) , CAMK1A (human) ( 6 ) , p90RSK (rat) ( 26 ) , Pim1 (human) ( 17 ) , RSK2 (mouse) ( 26 )
Kinases, in vitro:
Akt1 (human) ( 16 , 25 , 26 , 27 ) , AMPKA1 (human) ( 22 ) , p90RSK (rat) ( 26 ) , Pim1 (human) ( 17 ) , RSK2 (mouse) ( 26 ) , SGK1 (human) ( 18 )
Treatments:
A-443654 ( 14 ) , aflatoxin_B1 ( 11 ) , eflornithine ( 14 ) , glucose_starvation ( 22 ) , hypoxia ( 5 ) , LY294002 ( 14 , 16 , 24 , 25 ) , MG132 ( 22 ) , Nodal ( 7 ) , serum ( 16 ) , spermidine ( 14 )

Downstream Regulation
Effects of modification on p27Kip1:
intracellular localization ( 1 , 17 , 18 , 22 , 23 , 24 , 25 , 27 ) , molecular association, regulation ( 2 , 10 , 17 , 23 , 26 , 27 ) , protein degradation ( 11 , 17 ) , protein stabilization ( 3 , 22 , 23 )
Effects of modification on biological processes:
cell cycle regulation ( 3 , 17 , 22 , 23 , 27 ) , cell growth, altered ( 22 ) , cell motility, induced ( 2 , 10 ) , transcription, induced ( 2 )
Induce interaction with:
14-3-3 epsilon (human) ( 26 , 27 ) , 14-3-3 eta (human) ( 26 , 27 ) , 14-3-3 sigma (human) ( 26 ) , 14-3-3 theta (human) ( 17 , 26 , 27 ) , CDK4 (human) ( 23 ) , JAK2 (human) ( 2 ) , STMN1 (human) ( 10 )
Inhibit interaction with:
CDK2 (human) ( 23 )

Disease / Diagnostics Relevance
Relevant diseases:
kidney cancer ( 13 ) , anaplastic thyroid carcinoma ( 24 ) , follicular thyroid carcinoma ( 24 ) , papillary thyroid carcinoma ( 24 )

References 

1

Li Y, et al. (2016) p27 Is a Candidate Prognostic Biomarker and Metastatic Promoter in Osteosarcoma. Cancer Res 76, 4002-11
27197201   Curated Info

2

Zhao D, et al. (2015) Cytoplasmic p27 promotes epithelial-mesenchymal transition and tumor metastasis via STAT3-mediated Twist1 upregulation. Oncogene 34, 5447-59
25684140   Curated Info

3

Zhou N, et al. (2015) Role of dual specificity tyrosine-phosphorylation-regulated kinase 1B (Dyrk1B) in S-phase entry of HPV E7 expressing cells from quiescence. Oncotarget 6, 30745-30761
26307683   Curated Info

4

Wan C, et al. (2015) MIF4G domain containing protein regulates cell cycle and hepatic carcinogenesis by antagonizing CDK2-dependent p27 stability. Oncogene 34, 237-45
24336329   Curated Info

5

Högel H, Miikkulainen P, Bino L, Jaakkola PM (2015) Hypoxia inducible prolyl hydroxylase PHD3 maintains carcinoma cell growth by decreasing the stability of p27. Mol Cancer 14, 143
26223520   Curated Info

6

Mallampalli RK, et al. (2013) Fbxl12 triggers G1 arrest by mediating degradation of calmodulin kinase I. Cell Signal 25, 2047-59
23707388   Curated Info

7

Nadeem L, et al. (2013) Cytoplasmic mislocalization of p27 and CDK2 mediates the anti-migratory and anti-proliferative effects of Nodal in human trophoblast cells. J Cell Sci 126, 445-53
23230143   Curated Info

8

Fang Z, et al. (2012) Androgen Receptor Enhances p27 Degradation in Prostate Cancer Cells through Rapid and Selective TORC2 Activation. J Biol Chem 287, 2090-8
22139837   Curated Info

9

Pierantoni GM, et al. (2011) Homeodomain-interacting protein kinase-2 stabilizes p27(kip1) by its phosphorylation at serine 10 and contributes to cell motility. J Biol Chem 286, 29005-13
21715331   Curated Info

10

Schiappacassi M, et al. (2011) Role of T198 modification in the regulation of p27(Kip1) protein stability and function. PLoS One 6, e17673
21423803   Curated Info

11

Ranchal I, et al. (2009) The reduction of cell death and proliferation by p27(Kip1) minimizes DNA damage in an experimental model of genotoxicity. Int J Cancer 125, 2270-80
19672859   Curated Info

12

Possemato A (2009) CST Curation Set: 7128; Year: 2009; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: RXXp[ST]
Curated Info

13

Kim J, et al. (2009) Cytoplasmic sequestration of p27 via AKT phosphorylation in renal cell carcinoma. Clin Cancer Res 15, 81-90
19118035   Curated Info

14

Koomoa DL, et al. (2008) Ornithine decarboxylase inhibition by alpha-difluoromethylornithine activates opposing signaling pathways via phosphorylation of both Akt/protein kinase B and p27Kip1 in neuroblastoma. Cancer Res 68, 9825-31
19047162   Curated Info

15

Stokes M (2008) CST Curation Set: 5298; Year: 2008; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: RRXp[ST] Antibodies Used to Purify Peptides prior to LCMS: Phospho-PKA Substrate (RRXS/T) (100G7) Rabbit mAb Cat#: 9624, PTMScan(R) Phospho-PKA Substrate Motif (K/RK/RXS*/T*) Immunoaffinity Beads Cat#: 1984
Curated Info

16

Larrea MD, et al. (2008) Phosphorylation of p27Kip1 regulates assembly and activation of cyclin D1-Cdk4. Mol Cell Biol 28, 6462-72
18710949   Curated Info

17

Morishita D, et al. (2008) Pim kinases promote cell cycle progression by phosphorylating and down-regulating p27Kip1 at the transcriptional and posttranscriptional levels. Cancer Res 68, 5076-85
18593906   Curated Info

18

Hong F, et al. (2008) mTOR-raptor binds and activates SGK1 to regulate p27 phosphorylation. Mol Cell 30, 701-11
18570873   Curated Info

19

Rikova K (2008) CST Curation Set: 4327; Year: 2008; Biosample/Treatment: tissue, breast/untreated; Disease: breast cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: RXXp[ST] Antibodies Used to Purify Peptides prior to LCMS: Phospho-Akt Substrate (RXRXXS/T) (110B7) Rabbit mAb Cat#: 9614, PTMScan(R) Phospho-Akt Substrate Motif (RXXS*/T*) Immunoaffinity Beads Cat#: 1978
Curated Info

20

Ren H (2008) CST Curation Set: 4014; Year: 2008; Biosample/Treatment: tissue, gastrointestinal tract/untreated; Disease: gastric cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: RXXp[ST] Antibodies Used to Purify Peptides prior to LCMS: Phospho-Akt Substrate (RXRXXS/T) (110B7) Rabbit mAb Cat#: 9614, PTMScan(R) Phospho-Akt Substrate Motif (RXXS*/T*) Immunoaffinity Beads Cat#: 1978
Curated Info

21

Possemato A (2007) CST Curation Set: 2929; Year: 2007; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: RRXp[ST] Antibodies Used to Purify Peptides prior to LCMS: Phospho-PKA Substrate (RRXS/T) (100G7) Rabbit mAb Cat#: 9624, PTMScan(R) Phospho-PKA Substrate Motif (K/RK/RXS*/T*) Immunoaffinity Beads Cat#: 1984
Curated Info

22

Liang J, et al. (2007) The energy sensing LKB1-AMPK pathway regulates p27(kip1) phosphorylation mediating the decision to enter autophagy or apoptosis. Nat Cell Biol 9, 218-24
17237771   Curated Info

23

Kossatz U, et al. (2006) C-terminal phosphorylation controls the stability and function of p27kip1. EMBO J 25, 5159-70
17053782   Curated Info

24

Motti ML, et al. (2005) Complex regulation of the cyclin-dependent kinase inhibitor p27kip1 in thyroid cancer cells by the PI3K/AKT pathway: regulation of p27kip1 expression and localization. Am J Pathol 166, 737-49
15743786   Curated Info

25

Motti ML, et al. (2004) Akt-dependent T198 phosphorylation of cyclin-dependent kinase inhibitor p27kip1 in breast cancer. Cell Cycle 3, 1074-80
15280662   Curated Info

26

Fujita N, Sato S, Tsuruo T (2003) Phosphorylation of p27Kip1 at threonine 198 by p90 ribosomal protein S6 kinases promotes its binding to 14-3-3 and cytoplasmic localization. J Biol Chem 278, 49254-60
14504289   Curated Info

27

Fujita N, Sato S, Katayama K, Tsuruo T (2002) Akt-dependent phosphorylation of p27Kip1 promotes binding to 14-3-3 and cytoplasmic localization. J Biol Chem 277, 28706-13
12042314   Curated Info