Thr157
Javascript is not enabled on this browser. This site will not work properly without Javascript.
PhosphoSitePlus Homepage PhosphoSitePlus® v6.5.9.3
Powered by Cell Signaling Technology
Home > Phosphorylation Site Page: > Thr157  -  p27Kip1 (human)

Site Information
GIRkrPAtDDSSTQN   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 448645

In vivo Characterization
Methods used to characterize site in vivo:
[32P] bio-synthetic labeling ( 25 ) , immunoprecipitation ( 2 , 3 , 12 , 13 ) , mass spectrometry ( 10 ) , microscopy-colocalization with upstream kinase ( 15 , 25 ) , mutation of modification site ( 1 , 2 , 3 , 4 , 8 , 13 , 14 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ) , phospho-antibody ( 2 , 7 , 8 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 23 , 24 ) , phosphopeptide mapping ( 25 ) , western blotting ( 1 , 2 , 3 , 7 , 8 , 12 , 14 , 15 , 16 , 17 , 18 , 19 , 23 )
Disease tissue studied:
bone cancer ( 1 ) , osteosarcoma ( 1 ) , breast cancer ( 12 , 14 , 15 , 17 , 23 , 25 ) , leukemia ( 13 ) , chronic myelogenous leukemia ( 13 ) , lung cancer ( 17 ) , non-small cell lung cancer ( 17 ) , lymphoma ( 3 ) , prostate cancer ( 8 , 13 ) , melanoma skin cancer ( 14 ) , fibrosarcoma of soft tissue ( 3 ) , thyroid cancer ( 19 ) , anaplastic thyroid carcinoma ( 19 ) , follicular thyroid carcinoma ( 19 ) , papillary thyroid carcinoma ( 19 )
Relevant cell line - cell type - tissue:

Upstream Regulation
Regulatory protein:
Akt1 (human) ( 17 , 23 ) , Akt2 (human) ( 17 ) , Akt3 (human) ( 17 ) , EGLN3 (human) ( 5 ) , PCGF2 (human) ( 15 ) , PHLPP (human) ( 17 ) , PHLPP2 (human) ( 17 ) , Raptor (human) ( 14 ) , RICTOR (human) ( 14 ) , SGK1 (human) ( 14 ) , TSC2 (human) ( 14 )
Putative in vivo kinases:
Akt1 (human) ( 8 , 19 , 20 , 23 , 24 , 25 ) , CAMK1A (human) ( 6 ) , Pim1 (human) ( 13 ) , SGK1 (human) ( 14 )
Kinases, in vitro:
Akt1 (human) ( 12 , 23 , 24 , 25 ) , Pim1 (human) ( 13 ) , SGK1 (human) ( 14 )
Putative upstream phosphatases:
PPP2R5C (human) ( 2 )
Phosphatases, in vitro:
PPP2R5C (human) ( 2 )
Treatments:
Akt_inhibitor_VIII ( 8 ) , amino_acids ( 14 ) , androstanolone ( 8 ) , CTGF ( 18 ) , estradiol ( 14 ) , hypoxia ( 5 ) , insulin ( 14 ) , interleukin-6-hydroxymethyl-chiro-inositol-2(R)-2-methyl-3-O-octadecylcarbonate ( 18 ) , leptomycin_B ( 20 ) , LY294002 ( 11 , 12 , 15 , 18 , 19 , 23 , 24 , 25 ) , Nodal ( 7 ) , PD98059 ( 15 , 23 ) , rapamycin ( 11 , 14 ) , serum ( 12 , 20 ) , siRNA ( 14 , 17 ) , TGF-beta ( 16 ) , U0126 ( 23 , 25 ) , wortmannin ( 11 )

Downstream Regulation
Effects of modification on p27Kip1:
intracellular localization ( 2 , 3 , 11 , 13 , 14 , 15 , 18 , 19 , 20 , 22 , 23 , 24 , 25 ) , molecular association, regulation ( 4 , 12 , 13 , 20 , 22 ) , phosphorylation ( 25 ) , protein degradation ( 8 , 13 )
Effects of modification on biological processes:
apoptosis, inhibited ( 11 ) , cell cycle regulation ( 13 , 23 , 24 ) , cell growth, altered ( 25 ) , cell motility, induced ( 4 ) , cytoskeletal reorganization ( 18 ) , transcription, induced ( 4 )
Induce interaction with:
14-3-3 beta (human) ( 22 ) , 14-3-3 epsilon (human) ( 22 ) , 14-3-3 gamma (human) ( 22 ) , 14-3-3 theta (human) ( 13 ) , CCND1 (human) ( 12 ) , CDK4 (human) ( 12 ) , JAK2 (human) ( 4 ) , KPNA5 (human) ( 22 )
Inhibit interaction with:
KPNA1 (human) ( 20 )

Disease / Diagnostics Relevance
Relevant diseases:
breast cancer ( 3 ) , kidney cancer ( 11 ) , anaplastic thyroid carcinoma ( 19 ) , follicular thyroid carcinoma ( 19 ) , papillary thyroid carcinoma ( 19 )

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

Lai TY, et al. (2016) The B56γ3 regulatory subunit-containing protein phosphatase 2A outcompetes Akt to regulate p27KIP1 subcellular localization by selectively dephosphorylating phospho-Thr157 of p27KIP1. Oncotarget 7, 4542-58
26684356   Curated Info

3

Bahram F, et al. (2016) Interferon-γ-induced p27KIP1 binds to and targets MYC for proteasome-mediated degradation. Oncotarget 7, 2837-54
26701207   Curated Info

4

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

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

Guo A (2011) CST Curation Set: 12077; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pTDXEAntibodies Used to Purify Peptides prior to LCMS: Phospho(Ser/Thr) CK2 Substrate (P-S/T3-100) Rabbit mAb Cat#: 8738
Curated Info

11

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

12

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

13

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

14

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

15

Lee JY, et al. (2008) Mel-18 negatively regulates INK4a/ARF-independent cell cycle progression via Akt inactivation in breast cancer. Cancer Res 68, 4201-9
18519679   Curated Info

16

Kim SM, et al. (2007) TGF-beta1-induced PINCH-1-ILK-alpha-parvin complex formation regulates mesangial cell proliferation and hypertrophy. Exp Mol Med 39, 514-23
17934340   Curated Info

17

Brognard J, Sierecki E, Gao T, Newton AC (2007) PHLPP and a second isoform, PHLPP2, differentially attenuate the amplitude of Akt signaling by regulating distinct Akt isoforms. Mol Cell 25, 917-31
17386267   Curated Info

18

Crean JK, et al. (2006) Connective tissue growth factor/CCN2 stimulates actin disassembly through Akt/protein kinase B-mediated phosphorylation and cytoplasmic translocation of p27(Kip-1). FASEB J 20, 1712-4
16790529   Curated Info

19

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

20

Shin I, Rotty J, Wu FY, Arteaga CL (2005) Phosphorylation of p27Kip1 at Thr-157 interferes with its association with importin alpha during G1 and prevents nuclear re-entry. J Biol Chem 280, 6055-63
15579463   Curated Info

21

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

22

Sekimoto T, Fukumoto M, Yoneda Y (2004) 14-3-3 suppresses the nuclear localization of threonine 157-phosphorylated p27(Kip1). EMBO J 23, 1934-42
15057270   Curated Info

23

Viglietto G, et al. (2002) Cytoplasmic relocalization and inhibition of the cyclin-dependent kinase inhibitor p27(Kip1) by PKB/Akt-mediated phosphorylation in breast cancer. Nat Med 8, 1136-44
12244303   Curated Info

24

Liang J, et al. (2002) PKB/Akt phosphorylates p27, impairs nuclear import of p27 and opposes p27-mediated G1 arrest. Nat Med 8, 1153-60
12244302   Curated Info

25

Shin I, et al. (2002) PKB/Akt mediates cell-cycle progression by phosphorylation of p27(Kip1) at threonine 157 and modulation of its cellular localization. Nat Med 8, 1145-52
12244301   Curated Info