Ser516
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Home > Phosphorylation Site Page: > Ser516  -  Chk2 (human)

Site Information
PQVLAQPstSRKRPR   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 448840

In vivo Characterization
Methods used to characterize site in vivo:
[32P] bio-synthetic labeling ( 7 , 13 , 14 ) , electrophoretic mobility shift ( 7 ) , flow cytometry ( 2 ) , immunoprecipitation ( 2 ) , mass spectrometry ( 8 , 11 ) , mass spectrometry (in vitro) ( 9 ) , mutation of modification site ( 2 , 7 , 13 , 14 ) , peptide sequencing ( 13 ) , phospho-antibody ( 1 , 2 , 4 , 5 , 6 , 7 , 8 , 10 , 11 , 12 , 13 , 14 ) , phosphopeptide mapping ( 7 , 8 , 14 ) , western blotting ( 1 , 2 , 4 , 5 , 7 , 8 , 10 , 11 , 12 )
Disease tissue studied:
bone cancer ( 2 , 7 ) , breast cancer ( 1 , 12 ) , breast ductal carcinoma ( 1 ) , breast cancer, triple negative ( 1 ) , colorectal cancer ( 4 , 10 ) , colorectal carcinoma ( 4 , 10 ) , lung cancer ( 6 , 12 ) , non-small cell lung cancer ( 6 ) , pancreatic cancer ( 1 ) , pancreatic carcinoma ( 1 )
Relevant cell line - cell type - tissue:
293 (epithelial) ( 5 , 7 , 13 , 14 ) , A549 (pulmonary) ( 12 ) , CHO (fibroblast) ( 10 ) , DLD1 (intestinal) ( 4 ) , E.coli (bacterial) ( 8 , 11 ) , HCT116 (intestinal) ( 4 ) , HCT15 (intestinal) ( 10 , 13 ) , HEK293T (epithelial) ( 2 , 12 ) , HeLa (cervical) ( 2 , 14 ) , MCF-7 (breast cell) ( 12 ) , MDA-MB-231 (breast cell) ( 1 ) , MEF (fibroblast) ( 2 , 7 ) , MEF (fibroblast) [IGF1R (mouse)] ( 14 ) , NCI-H460 (pulmonary) ( 6 ) , SF9 ( 8 , 13 ) , U2OS (bone cell) ( 2 , 7 )

Upstream Regulation
Regulatory protein:
Chk2 (human) ( 12 ) , FBXW7 (human) ( 4 )
Putative in vivo kinases:
Chk2 (human) ( 7 , 13 , 14 )
Kinases, in vitro:
Chk2 (human) ( 7 , 8 , 13 , 14 )
Phosphatases, in vitro:
PPM1D (human) ( 10 ) , PPPM1A (human) ( 10 )
Treatments:
2-deoxyglucose ( 6 ) , Chk2_inhibitor_II ( 1 ) , gemcitabine ( 1 ) , ionizing_radiation ( 5 , 12 , 13 , 14 ) , MK-8776 ( 1 )

Downstream Regulation
Effects of modification on Chk2:
enzymatic activity, induced ( 13 , 14 )
Effects of modification on biological processes:
cell cycle regulation ( 1 )

References 

1

Warren N, Eastman A (2018) Inhibition of checkpoint kinase 1 following gemcitabine-mediated S phase arrest results in CDC7- and CDK2-dependent replication catastrophe. J Biol Chem
30573684   Curated Info

2

García-Limones C, et al. (2016) CHK2 stability is regulated by the E3 ubiquitin ligase SIAH2. Oncogene 35, 4289-301
26751770   Curated Info

3

Agarwal S, Bell CM, Rothbart SB, Moran RG (2015) AMP-activated Protein Kinase (AMPK) Control of mTORC1 Is p53- and TSC2-independent in Pemetrexed-treated Carcinoma Cells. J Biol Chem 290, 27473-86
26391395   Curated Info

4

Li N, et al. (2015) FBXW7-mutated colorectal cancer cells exhibit aberrant expression of phosphorylated-p53 at Serine-15. Oncotarget 6, 9240-56
25860929   Curated Info

5

Guo X, et al. (2010) Interdependent phosphorylation within the kinase domain T-loop Regulates CHK2 activity. J Biol Chem 285, 33348-57
20713355   Curated Info

6

Zhong D, et al. (2009) The Glycolytic Inhibitor 2-Deoxyglucose Activates Multiple Prosurvival Pathways through IGF1R. J Biol Chem 284, 23225-33
19574224   Curated Info

7

Lovly CM, et al. (2008) Regulation of Chk2 ubiquitination and signaling through autophosphorylation of serine 379. Mol Cell Biol 28, 5874-85
18644861   Curated Info

8

Gabant G, et al. (2008) Autophosphorylated residues involved in the regulation of human chk2 in vitro. J Mol Biol 380, 489-503
18538787   Curated Info

9

Kass EM, et al. (2007) Stability of checkpoint kinase 2 is regulated via phosphorylation at serine 456. J Biol Chem 282, 30311-21
17715138   Curated Info

10

Oliva-Trastoy M, et al. (2007) The Wip1 phosphatase (PPM1D) antagonizes activation of the Chk2 tumour suppressor kinase. Oncogene 26, 1449-58
16936775   Curated Info

11

King JB, et al. (2007) Identification of protein phosphorylation sites within Ser/Thr-rich cluster domains using site-directed mutagenesis and hybrid linear quadrupole ion trap Fourier transform ion cyclotron resonance mass spectrometry. Rapid Commun Mass Spectrom 21, 3443-51
17918214   Curated Info

12

Yoda A, et al. (2006) Intrinsic kinase activity and SQ/TQ domain of Chk2 kinase as well as N-terminal domain of Wip1 phosphatase are required for regulation of Chk2 by Wip1. J Biol Chem 281, 24847-62
16798742   Curated Info

13

Wu X, Chen J (2003) Autophosphorylation of checkpoint kinase 2 at serine 516 is required for radiation-induced apoptosis. J Biol Chem 278, 36163-8
12855706   Curated Info

14

Schwarz JK, Lovly CM, Piwnica-Worms H (2003) Regulation of the Chk2 protein kinase by oligomerization-mediated cis- and trans-phosphorylation. Mol Cancer Res 1, 598-609
12805407   Curated Info

15

Lou Z, Minter-Dykhouse K, Wu X, Chen J (2003) MDC1 is coupled to activated CHK2 in mammalian DNA damage response pathways. Nature 421, 957-61
12607004   Curated Info

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