Ser428
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Home > Phosphorylation Site Page: > Ser428  -  LKB1 (human)

Site Information
SSkIRRLsACkQQ__   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 448147

In vivo Characterization
Methods used to characterize site in vivo:
mass spectrometry ( 7 , 8 , 9 ) , mutation of modification site ( 11 , 16 , 19 ) , phospho-antibody ( 1 , 2 , 3 , 4 , 5 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ) , western blotting ( 1 , 2 , 3 , 4 , 5 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 )
Disease tissue studied:
bone cancer ( 1 , 3 ) , breast cancer ( 16 ) , cervical cancer ( 14 , 16 , 18 , 19 ) , cervical adenocarcinoma ( 14 , 16 , 18 , 19 ) , liver cancer ( 15 ) , lung cancer ( 2 , 11 , 14 , 18 , 19 ) , non-small cell lung cancer ( 2 ) , non-small cell lung adenocarcinoma ( 2 ) , non-small cell large cell lung carcinoma ( 2 ) , ovarian cancer ( 4 ) , pancreatic cancer ( 10 ) , pancreatic carcinoma ( 10 )
Relevant cell line - cell type - tissue:

Upstream Regulation
Regulatory protein:
EGFR (human) ( 13 ) , IHPK1 (human) ( 5 ) , IHPK2 (human) ( 5 ) , LKB1 (human) ( 17 ) , PKCZ (human) ( 14 , 16 , 19 )
Putative in vivo kinases:
PKACA (human) ( 2 ) , PKCZ (human) ( 11 , 19 )
Kinases, in vitro:
LKB1 (human) ( 16 ) , PKCZ (human) ( 16 , 19 )
Putative upstream phosphatases:
PPP2CA (human) ( 3 )
Treatments:
2-deoxyglucose ( 11 ) , acadesine ( 11 , 15 , 18 ) , AG1478 ( 13 ) , atenolol ( 2 ) , BAPTA-AM ( 14 ) , colforsin ( 12 ) , EGF ( 13 ) , H-89 ( 2 ) , H2O2 ( 13 ) , ICI-118,551 ( 2 ) , leptin ( 11 ) , metformin ( 11 ) , NAC ( 13 ) , nicotine ( 17 ) , NNAL ( 2 ) , NNK ( 2 ) , okadaic_acid ( 3 , 18 ) , ONOO(-) ( 11 , 16 , 18 , 19 ) , palmitate ( 18 ) , PD153035 ( 13 ) , PDTC ( 13 ) , phenoxybenzamine ( 2 ) , phorbol_ester ( 19 ) , PKC-zeta_inhibitor ( 11 , 16 , 19 ) , propranolol ( 2 ) , PyST ( 3 ) , resveratrol ( 15 ) , S17834 ( 15 ) , simvastatin ( 14 ) , Sin-1 ( 16 ) , siRNA ( 11 , 16 ) , statin ( 11 ) , STO-609 ( 14 ) , UV ( 13 ) , yohimbine ( 2 )

Downstream Regulation
Effects of modification on LKB1:
enzymatic activity, induced ( 3 , 19 ) , intracellular localization ( 11 , 16 ) , molecular association, regulation ( 11 ) , phosphorylation ( 3 , 16 , 19 )
Effects of modification on biological processes:
carcinogenesis, induced ( 2 ) , carcinogenesis, inhibited ( 3 ) , cell cycle regulation ( 3 ) , cell growth, altered ( 11 ) , cell motility, induced ( 2 ) , signaling pathway regulation ( 3 )
Induce interaction with:
Exportin-1 (human) ( 11 ) , STRAD (human) ( 11 )

Disease / Diagnostics Relevance
Relevant diseases:
lung cancer ( 2 ) , ovarian epithelial carcinoma ( 4 )

References 

1

Tan I, et al. (2023) Identification of a novel mitochondria-localized LKB1 variant required for the regulation of the oxidative stress response. J Biol Chem 299, 104906
37302555   Curated Info

2

Bian T, et al. (2022) LKB1 phosphorylation and deactivation in lung cancer by NNAL, a metabolite of tobacco-specific carcinogen, in an isomer-dependent manner. Oncogene
35835853   Curated Info

3

Sarwar Z, et al. (2021) Interaction of DBC1 with polyoma small T antigen promotes its degradation and negatively regulates tumorigenesis. J Biol Chem, 101496
34921839   Curated Info

4

Peart T, et al. (2015) Intact LKB1 activity is required for survival of dormant ovarian cancer spheroids. Oncotarget 6, 22424-38
26068970   Curated Info

5

Rao F, et al. (2015) Inositol pyrophosphates promote tumor growth and metastasis by antagonizing liver kinase B1. Proc Natl Acad Sci U S A 112, 1773-8
25617365   Curated Info

6

Zhu H, et al. (2013) Phosphorylation of serine 399 in LKB1 protein short form by protein kinase Cζ is required for its nucleocytoplasmic transport and consequent AMP-activated protein kinase (AMPK) activation. J Biol Chem 288, 16495-505
23612973   Curated Info

7

Mulhern D (2012) CST Curation Set: 13107; Year: 2012; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

8

Mulhern D (2012) CST Curation Set: 13108; Year: 2012; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

9

Mulhern D (2011) CST Curation Set: 13106; 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: p[STY])
Curated Info

10

Garcia-Haro L, et al. (2010) The PP1-R6 protein phosphatase holoenzyme is involved in the glucose-induced dephosphorylation and inactivation of AMP-activated protein kinase, a key regulator of insulin secretion, in MIN6 beta cells. FASEB J 24, 5080-91
20724523   Curated Info

11

Xie Z, et al. (2009) Identification of the serine 307 of LKB1 as a novel phosphorylation site essential for its nucleocytoplasmic transport and endothelial cell angiogenesis. Mol Cell Biol 29, 3582-96
19414597   Curated Info

12

Denison FC, Hiscock NJ, Carling D, Woods A (2009) Characterization of an alternative splice variant of LKB1. J Biol Chem 284, 67-76
18854309   Curated Info

13

Cao C, et al. (2008) AMP-activated protein kinase contributes to UV- and H2O2-induced apoptosis in human skin keratinocytes. J Biol Chem 283, 28897-908
18715874   Curated Info

14

Choi HC, et al. (2008) Reactive nitrogen species is required for the activation of the AMP-activated protein kinase by statin in vivo. J Biol Chem 283, 20186-97
18474592   Curated Info

15

Hou X, et al. (2008) SIRT1 regulates hepatocyte lipid metabolism through activating AMP-activated protein kinase. J Biol Chem 283, 20015-26
18482975   Curated Info

16

Song P, et al. (2008) Protein kinase Czeta-dependent LKB1 serine 428 phosphorylation increases LKB1 nucleus export and apoptosis in endothelial cells. J Biol Chem 283, 12446-55
18321849   Curated Info

17

An Z, et al. (2007) Nicotine-induced activation of AMP-activated protein kinase inhibits fatty acid synthase in 3T3L1 adipocytes: a role for oxidant stress. J Biol Chem 282, 26793-801
17635921   Curated Info

18

Wu Y, et al. (2007) Activation of protein phosphatase 2A by palmitate inhibits AMP-activated protein kinase. J Biol Chem 282, 9777-88
17255104   Curated Info

19

Xie Z, et al. (2006) Activation of protein kinase C zeta by peroxynitrite regulates LKB1-dependent AMP-activated protein kinase in cultured endothelial cells. J Biol Chem 281, 6366-75
16407220   Curated Info