Ser69
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Home > Phosphorylation Site Page: > Ser69  -  BIM (human)

Site Information
GPLAPPAsPGPFATR   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 449330

In vivo Characterization
Methods used to characterize site in vivo:
[32P] bio-synthetic labeling ( 11 ) , electrophoretic mobility shift ( 8 , 11 ) , immunoprecipitation ( 2 ) , mutation of modification site ( 1 , 3 , 5 , 8 , 9 , 10 , 11 ) , phospho-antibody ( 1 , 2 , 3 , 6 , 7 , 8 , 9 , 10 ) , western blotting ( 1 , 2 , 3 , 6 , 7 , 8 , 9 , 10 )
Disease tissue studied:
breast cancer ( 9 , 10 ) , leukemia ( 6 , 11 ) , acute lymphocytic leukemia ( 6 ) , chronic myelogenous leukemia ( 11 ) , T cell leukemia ( 6 ) , lung cancer ( 1 , 2 ) , non-small cell lung cancer ( 1 , 2 ) , non-small cell lung adenocarcinoma ( 1 , 2 ) , lymphoma ( 11 ) , Burkitt's lymphoma ( 11 ) , fibrosarcoma of soft tissue ( 7 )
Relevant cell line - cell type - tissue:

Upstream Regulation
Regulatory protein:
ERK1 (human) ( 1 ) , ERK2 (human) ( 1 ) , LIMS1 (human) ( 7 ) , PXN (human) ( 1 )
Putative in vivo kinases:
ERK1 (human) ( 8 , 11 ) , ERK2 (human) ( 8 )
Kinases, in vitro:
ERK1 (human) ( 11 ) , ERK2 (human) ( 9 )
Treatments:
gefitinib ( 2 ) , GF109203X ( 11 ) , LY294002 ( 11 ) , MG132 ( 1 , 6 ) , nocodazole ( 3 ) , phorbol_ester ( 9 , 11 ) , RO-3306 ( 3 ) , SB203580 ( 11 ) , tamoxifen ( 11 ) , U0126 ( 8 , 9 , 11 )

Downstream Regulation
Effects of modification on BIM:
molecular association, regulation ( 8 ) , protein degradation ( 1 , 8 , 9 , 11 )
Effects of modification on biological processes:
apoptosis, altered ( 5 , 8 ) , apoptosis, inhibited ( 1 , 11 ) , cell adhesion, altered ( 5 ) , transcription, altered ( 5 )
Inhibit interaction with:
Bcl-xL (human) ( 8 ) , MCL1 (human) ( 8 )

References 

1

Wu DW, Chen CY, Chu CL, Lee H (2016) Paxillin confers resistance to tyrosine kinase inhibitors in EGFR-mutant lung cancers via modulating BIM and Mcl-1 protein stability. Oncogene 35, 621-30
25915848   Curated Info

2

Phuchareon J, McCormick F, Eisele DW, Tetsu O (2015) EGFR inhibition evokes innate drug resistance in lung cancer cells by preventing Akt activity and thus inactivating Ets-1 function. Proc Natl Acad Sci U S A 112, E3855-63
26150526   Curated Info

3

Moustafa-Kamal M, et al. (2013) BimEL is phosphorylated at mitosis by Aurora A and targeted for degradation by ╬▓TrCP1. Cell Death Differ 20, 1393-403
23912711   Curated Info

4

Gilley R, et al. (2012) CDK1, not ERK1/2 or ERK5, is required for mitotic phosphorylation of BIM(EL). Cell Signal 24, 170-80
21924351   Curated Info

5

Boisvert-Adamo K, Aplin AE (2008) Mutant B-RAF mediates resistance to anoikis via Bad and Bim. Oncogene 27, 3301-12
18246127   Curated Info

6

Leung KT, et al. (2008) Activation of the JNK pathway promotes phosphorylation and degradation of BimEL--a novel mechanism of chemoresistance in T-cell acute lymphoblastic leukemia. Carcinogenesis 29, 544-51
18174237   Curated Info

7

Chen K, et al. (2008) PINCH-1 regulates the ERK-Bim pathway and contributes to apoptosis resistance in cancer cells. J Biol Chem 283, 2508-17
18063582   Curated Info

8

Ewings KE, et al. (2007) ERK1/2-dependent phosphorylation of BimEL promotes its rapid dissociation from Mcl-1 and Bcl-xL. EMBO J 26, 2856-67
17525735   Curated Info

9

Fukazawa H, et al. (2004) BimEL is an important determinant for induction of anoikis sensitivity by mitogen-activated protein/extracellular signal-regulated kinase kinase inhibitors. Mol Cancer Ther 3, 1281-8
15486195   Curated Info

10

Marani M, et al. (2004) Role of Bim in the survival pathway induced by Raf in epithelial cells. Oncogene 23, 2431-41
14676826   Curated Info

11

Luciano F, et al. (2003) Phosphorylation of Bim-EL by Erk1/2 on serine 69 promotes its degradation via the proteasome pathway and regulates its proapoptotic function. Oncogene 22, 6785-93
14555991   Curated Info