Ser10
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Home > Phosphorylation Site Page: > Ser10  -  p27Kip1 (human)

Site Information
NVRVSNGsPsLErMD   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447874

In vivo Characterization
Methods used to characterize site in vivo:
2D analysis ( 35 ) , [32P] bio-synthetic labeling ( 41 , 46 , 50 , 52 , 53 ) , electrophoretic mobility shift ( 48 , 53 ) , flow cytometry ( 1 ) , immunoassay ( 17 ) , immunoprecipitation ( 1 , 10 , 28 , 29 , 30 ) , mass spectrometry ( 1 , 2 , 4 , 6 , 11 , 12 , 13 , 15 , 18 , 19 , 20 , 22 , 24 , 26 , 32 , 42 ) , microscopy-colocalization with upstream kinase ( 31 ) , mutation of modification site ( 1 , 3 , 7 , 10 , 17 , 21 , 23 , 25 , 28 , 31 , 35 , 36 , 39 , 40 , 41 , 43 , 45 , 47 , 48 , 49 , 50 , 51 , 52 , 53 ) , phospho-antibody ( 5 , 8 , 9 , 10 , 17 , 21 , 23 , 25 , 27 , 29 , 30 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 43 , 45 , 46 , 49 , 50 , 52 ) , phosphoamino acid analysis ( 41 , 53 ) , phosphopeptide mapping ( 50 , 52 , 53 ) , western blotting ( 1 , 3 , 5 , 7 , 8 , 9 , 10 , 17 , 21 , 23 , 25 , 27 , 28 , 29 , 30 , 31 , 33 , 34 , 35 , 36 , 37 , 39 , 45 )
Disease tissue studied:
bone cancer ( 3 , 23 , 36 ) , osteosarcoma ( 3 ) , brain cancer ( 35 , 41 ) , astrocytoma ( 41 ) , glioblastoma ( 35 ) , glioblastoma multiforme ( 35 ) , glioma ( 35 ) , breast cancer ( 12 , 20 , 30 , 45 ) , breast ductal carcinoma ( 12 ) , HER2 positive breast cancer ( 4 ) , luminal A breast cancer ( 4 ) , luminal B breast cancer ( 4 ) , breast cancer, surrounding tissue ( 4 ) , breast cancer, triple negative ( 4 , 12 ) , leukemia ( 36 ) , chronic myelogenous leukemia ( 36 ) , liver cancer ( 1 , 27 , 31 ) , lung cancer ( 15 , 20 , 23 ) , non-small cell lung cancer ( 20 , 23 ) , non-small cell lung adenocarcinoma ( 15 ) , neuroblastoma ( 19 , 29 ) , ovarian cancer ( 12 ) , pancreatic ductal adenocarcinoma ( 13 ) , prostate cancer ( 21 ) , melanoma skin cancer ( 6 ) , thyroid cancer ( 39 ) , anaplastic thyroid carcinoma ( 39 ) , follicular thyroid carcinoma ( 39 ) , papillary thyroid carcinoma ( 39 )
Relevant cell line - cell type - tissue:
'muscle, skeletal' ( 22 ) , 'muscle, smooth'-'heart, artery' ( 9 ) , 'pancreatic, ductal'-pancreas ( 13 ) , 267B1 (epithelial) ( 10 ) , 293 (epithelial) [AT1 (human), transfection, AT1R stable transfected HEK293] ( 26 ) , 293 (epithelial) ( 23 , 28 , 37 , 43 , 50 ) , 3T3 (fibroblast) [SHP-2 (mouse), homozygous knockout] ( 40 , 48 , 50 , 51 , 52 , 53 ) , BC-1 (B lymphocyte) ( 36 ) , breast ( 4 , 12 ) , BT-474 (breast cell) ( 40 , 45 ) , BT-549 (breast cell) ( 20 ) , CHO (fibroblast) ( 35 ) , corneal ( 33 ) , COS (fibroblast) ( 53 ) , CWR22Rv1 (prostate cell) ( 21 ) , Dunn (osteoblast) ( 3 ) , H2077 (pulmonary) ( 20 ) , H322M (pulmonary) ( 20 ) , HCC366 (pulmonary) ( 20 ) , HCC78 (pulmonary) ( 20 ) , HDE-14 (lymphoblastoid) ( 38 ) , HEK293T (epithelial) [Akt1 (human)] ( 49 ) , HEK293T (epithelial) [p27Kip1 (human)] ( 49 ) , HEK293T (epithelial) ( 40 , 53 ) , HeLa (cervical) ( 2 , 8 , 10 , 11 , 18 , 24 , 25 , 40 , 42 , 52 , 53 ) , HepG2 (hepatic) ( 1 , 27 , 31 , 46 ) , HMEC (endothelial) ( 30 ) , HOP62 (pulmonary) ( 20 ) , hTERT-RPE1 (epithelial) ( 5 ) , HTR8/SVneo (trophoblast) ( 17 ) , IMR-90 (fibroblast) ( 35 ) , Jurkat (T lymphocyte) ( 32 ) , K7M2 (osteoblast) ( 3 ) , keratinocyte-skin ( 5 ) , LAN-1 (neural crest) ( 29 ) , lung ( 15 ) , MCF-7 (breast cell) ( 30 , 47 , 52 ) , MDA-MB-231 (breast cell) ( 20 ) , MDA-MB-468 (breast cell) ( 43 ) , MEF (fibroblast) [PIN1 (human), transfection] ( 28 ) , mesangial ( 34 ) , NB10 (neural crest) ( 19 ) , NCI-H1299 (pulmonary) ( 23 ) , NCI-H1395 (pulmonary) ( 20 ) , NCI-H157 (pulmonary) ( 20 ) , NCI-H1666 (pulmonary) ( 20 ) , NCI-H2030 (pulmonary) ( 20 ) , NCI-H322 (pulmonary) ( 20 ) , NCI-H520 (squamous) ( 20 ) , NPC (neural crest) ( 19 ) , ovary ( 12 ) , PC9 (pulmonary) ( 20 ) , Rat1 (fibroblast) ( 52 ) , Saos-2 (bone cell) ( 3 , 23 ) , SF9 ( 35 ) , SKBr3 (breast cell) ( 45 ) , T98G (glial) ( 35 ) , thyroid ( 35 , 39 ) , TPC-1 (thyroid cell) ( 39 ) , U2OS (bone cell) [GR (human)] ( 48 ) , U2OS (bone cell) ( 36 ) , U87MG (glial) ( 41 ) , WM239A (melanocyte) ( 6 )

Upstream Regulation
Regulatory protein:
DYRK1B (human) ( 5 ) , EGLN3 (human) ( 8 ) , MARCKS (human) ( 9 ) , MIF4GD (human) ( 7 )
Putative in vivo kinases:
Akt1 (human) ( 37 ) , CDK16 (human) ( 10 ) , HIPK2 (human) ( 23 ) , KIS (human) ( 50 )
Kinases, in vitro:
Akt1 (human) ( 37 , 44 , 49 ) , CAMK2A (human) ( 25 ) , CDK16 (human) ( 10 ) , CDK6 (human) ( 36 ) , ERK2 (human) ( 52 , 53 ) , HIPK2 (human) ( 23 ) , KIS (human) ( 50 ) , p90RSK (rat) ( 44 ) , RSK2 (mouse) ( 44 )
Treatments:
A-443654 ( 29 , 37 ) , aflatoxin_B1 ( 27 ) , anti-HER2 ( 45 ) , CTGF ( 34 ) , cycloheximide ( 23 ) , eflornithine ( 29 ) , FGF2 ( 33 ) , H2O2 ( 37 ) , HGF ( 46 ) , hypoxia ( 8 ) , LY294002 ( 29 , 30 , 33 , 41 , 43 ) , MG132 ( 23 ) , Nodal ( 17 ) , oncostatin_M ( 31 ) , oxidative_stress ( 37 ) , PD98059 ( 31 , 53 ) , PUGNAc ( 1 ) , retinoic_acid ( 38 ) , serum ( 30 , 37 , 48 ) , serum_starvation ( 50 ) , serum_withdrawal ( 37 ) , siRNA ( 10 ) , spermidine ( 29 ) , tamoxifen ( 52 ) , wortmannin ( 37 )

Downstream Regulation
Effects of modification on p27Kip1:
intracellular localization ( 3 , 9 , 17 , 25 , 31 , 36 , 40 , 46 , 47 , 50 , 51 , 52 ) , molecular association, regulation ( 31 , 51 ) , phosphorylation ( 1 , 40 ) , protein degradation ( 9 , 10 , 27 ) , protein stabilization ( 5 , 8 , 23 , 25 , 50 , 53 )
Effects of modification on biological processes:
apoptosis, inhibited ( 10 , 25 ) , carcinogenesis, induced ( 10 ) , cell adhesion, induced ( 31 ) , cell cycle regulation ( 5 , 10 , 45 , 48 , 50 ) , cell growth, induced ( 10 ) , cell motility, induced ( 3 , 23 ) , cytoskeletal reorganization ( 31 ) , transcription, altered ( 48 )
Induce interaction with:
Exportin-1 (human) ( 51 )
Inhibit interaction with:
CTNNB1 (human) ( 31 )

Disease / Diagnostics Relevance
Relevant diseases:
breast cancer ( 10 )

References 

1

Qiu H, et al. (2017) Modification of p27 with O-linked N-acetylglucosamine regulates cell proliferation in hepatocellular carcinoma. Mol Carcinog 56, 258-271
27175940   Curated Info

2

Huang H, et al. (2016) Simultaneous Enrichment of Cysteine-containing Peptides and Phosphopeptides Using a Cysteine-specific Phosphonate Adaptable Tag (CysPAT) in Combination with titanium dioxide (TiO2) Chromatography. Mol Cell Proteomics 15, 3282-3296
27281782   Curated Info

3

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

4

Mertins P, et al. (2016) Proteogenomics connects somatic mutations to signalling in breast cancer. Nature 534, 55-62
27251275   Curated Info

5

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

6

Stuart SA, et al. (2015) A Phosphoproteomic Comparison of B-RAFV600E and MKK1/2 Inhibitors in Melanoma Cells. Mol Cell Proteomics 14, 1599-615
25850435   Curated Info

7

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

8

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

9

Yu D, et al. (2015) MARCKS Signaling Differentially Regulates Vascular Smooth Muscle and Endothelial Cell Proliferation through a KIS-, p27kip1- Dependent Mechanism. PLoS One 10, e0141397
26528715   Curated Info

10

Yanagi T, Krajewska M, Matsuzawa S, Reed JC (2014) PCTAIRE1 phosphorylates p27 and regulates mitosis in cancer cells. Cancer Res 74, 5795-807
25205104   Curated Info

11

Sharma K, et al. (2014) Ultradeep human phosphoproteome reveals a distinct regulatory nature of Tyr and Ser/Thr-based signaling. Cell Rep 8, 1583-94
25159151   Curated Info

12

Mertins P, et al. (2014) Ischemia in tumors induces early and sustained phosphorylation changes in stress kinase pathways but does not affect global protein levels. Mol Cell Proteomics 13, 1690-704
24719451   Curated Info

13

Britton D, et al. (2014) Quantification of pancreatic cancer proteome and phosphorylome: indicates molecular events likely contributing to cancer and activity of drug targets. PLoS One 9, e90948
24670416   Curated Info

14

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

15

Schweppe DK, Rigas JR, Gerber SA (2013) Quantitative phosphoproteomic profiling of human non-small cell lung cancer tumors. J Proteomics 91, 286-96
23911959   Curated Info

16

Shiromizu T, et al. (2013) Identification of missing proteins in the neXtProt database and unregistered phosphopeptides in the PhosphoSitePlus database as part of the Chromosome-centric Human Proteome Project. J Proteome Res 12, 2414-21
23312004   Curated Info

17

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

18

Zhou H, et al. (2013) Toward a comprehensive characterization of a human cancer cell phosphoproteome. J Proteome Res 12, 260-71
23186163   Curated Info

19

DeNardo BD, et al. (2013) Quantitative phosphoproteomic analysis identifies activation of the RET and IGF-1R/IR signaling pathways in neuroblastoma. PLoS One 8, e82513
24349301   Curated Info

20

Klammer M, et al. (2012) Phosphosignature predicts dasatinib response in non-small cell lung cancer. Mol Cell Proteomics 11, 651-68
22617229   Curated Info

21

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

22

Lundby A, et al. (2012) Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues. Nat Commun 3, 876
22673903   Curated Info

23

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

24

Hegemann B, et al. (2011) Systematic phosphorylation analysis of human mitotic protein complexes. Sci Signal 4, rs12
22067460   Curated Info

25

Kajihara R, et al. (2010) CaMKII phosphorylates serine 10 of p27 and confers apoptosis resistance to HeLa cells. Biochem Biophys Res Commun 401, 350-5
20851109   Curated Info

26

Christensen GL, et al. (2010) Quantitative phosphoproteomics dissection of seven-transmembrane receptor signaling using full and biased agonists. Mol Cell Proteomics 9, 1540-53
20363803   Curated Info

27

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

28

Zhou W, et al. (2009) Pin1 catalyzes conformational changes of Thr-187 in p27Kip1 and mediates its stability through a polyubiquitination process. J Biol Chem 284, 23980-8
19584057   Curated Info

29

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

30

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

31

Théard D, et al. (2008) Formation of E-cadherin/beta-catenin-based adherens junctions in hepatocytes requires serine-10 in p27(Kip1). Mol Biol Cell 19, 1605-13
18272788   Curated Info

32

Stokes M (2008) CST Curation Set: 3885; Year: 2008; Biosample/Treatment: cell line, Jurkat/pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

33

Lee JG, Kay EP (2007) Two populations of p27 use differential kinetics to phosphorylate Ser-10 and Thr-187 via phosphatidylinositol 3-Kinase in response to fibroblast growth factor-2 stimulation. J Biol Chem 282, 6444-54
17209046   Curated Info

34

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

35

Bockstaele L, et al. (2006) Regulated activating Thr172 phosphorylation of cyclin-dependent kinase 4(CDK4): its relationship with cyclins and CDK "inhibitors". Mol Cell Biol 26, 5070-85
16782892   Curated Info

36

Sarek G, Järviluoma A, Ojala PM (2006) KSHV viral cyclin inactivates p27KIP1 through Ser10 and Thr187 phosphorylation in proliferating primary effusion lymphomas. Blood 107, 725-32
16160006   Curated Info

37

Nacusi LP, Sheaff RJ (2006) Akt1 sequentially phosphorylates p27kip1 within a conserved but non-canonical region. Cell Div 1, 11
16780593   Curated Info

38

Zancai P, et al. (2005) Retinoic acid stabilizes p27Kip1 in EBV-immortalized lymphoblastoid B cell lines through enhanced proteasome-dependent degradation of the p45Skp2 and Cks1 proteins. Oncogene 24, 2483-94
15735731   Curated Info

39

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

40

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

41

Brandts CH, et al. (2005) Phosphorylation-independent stabilization of p27kip1 by the phosphoinositide 3-kinase pathway in glioblastoma cells. J Biol Chem 280, 2012-9
15542603   Curated Info

42

Beausoleil SA, et al. (2004) Large-scale characterization of HeLa cell nuclear phosphoproteins. Proc Natl Acad Sci U S A 101, 12130-5
15302935   Curated Info

43

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

44

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

45

Le XF, et al. (2003) The role of cyclin-dependent kinase inhibitor p27Kip1 in anti-HER2 antibody-induced G1 cell cycle arrest and tumor growth inhibition. J Biol Chem 278, 23441-50
12700233   Curated Info

46

McAllister SS, et al. (2003) Novel p27(kip1) C-terminal scatter domain mediates Rac-dependent cell migration independent of cell cycle arrest functions. Mol Cell Biol 23, 216-28
12482975   Curated Info

47

Connor MK, et al. (2003) CRM1/Ran-mediated nuclear export of p27(Kip1) involves a nuclear export signal and links p27 export and proteolysis. Mol Biol Cell 14, 201-13
12529437   Curated Info

48

Chopra S, Fernandez De Mattos S, Lam EW, Mann DJ (2002) Jab1 co-activation of c-Jun is abrogated by the serine 10-phosphorylated form of p27Kip1. J Biol Chem 277, 32413-6
12119282   Curated Info

49

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

50

Boehm M, et al. (2002) A growth factor-dependent nuclear kinase phosphorylates p27(Kip1) and regulates cell cycle progression. EMBO J 21, 3390-401
12093740   Curated Info

51

Ishida N, et al. (2002) Phosphorylation of p27Kip1 on serine 10 is required for its binding to CRM1 and nuclear export. J Biol Chem 277, 14355-8
11889117   Curated Info

52

Rodier G, et al. (2001) p27 cytoplasmic localization is regulated by phosphorylation on Ser10 and is not a prerequisite for its proteolysis. EMBO J 20, 6672-82
11726503   Curated Info

53

Ishida N, Kitagawa M, Hatakeyama S, Nakayama K (2000) Phosphorylation at serine 10, a major phosphorylation site of p27(Kip1), increases its protein stability. J Biol Chem 275, 25146-54
10831586   Curated Info