Ser70
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Home > Phosphorylation Site Page: > Ser70  -  Bcl-2 (human)

Site Information
RDPVARtsPLQtPAA   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 448395

In vivo Characterization
Methods used to characterize site in vivo:
2D analysis ( 25 ) , [32P] bio-synthetic labeling ( 19 , 21 , 25 , 27 ) , electrophoretic mobility shift ( 24 , 25 ) , immunoassay ( 2 ) , immunoprecipitation ( 6 ) , microscopy-colocalization with upstream kinase ( 11 ) , mutation of modification site ( 6 , 8 , 10 , 12 , 13 , 15 , 17 , 19 , 21 , 22 , 23 , 24 , 25 , 26 , 28 , 29 ) , peptide sequencing ( 25 ) , phospho-antibody ( 2 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 14 , 16 , 18 , 20 , 22 , 30 ) , phosphoamino acid analysis ( 25 ) , western blotting ( 2 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 14 , 18 , 29 , 30 )
Disease tissue studied:
bladder cancer ( 5 ) , brain cancer ( 2 ) , glioblastoma ( 2 ) , glioma ( 2 ) , breast cancer ( 8 , 10 , 12 ) , colorectal cancer ( 8 , 9 ) , colorectal carcinoma ( 8 , 9 ) , leukemia ( 13 , 15 , 26 ) , acute lymphocytic leukemia ( 26 ) , lung cancer ( 9 , 14 , 15 , 16 , 20 , 21 ) , non-small cell lung cancer ( 9 , 15 ) , non-small cell squamous cell lung carcinoma ( 9 ) , small-cell lung cancer ( 20 , 21 ) , prostate cancer ( 7 , 26 , 30 )
Relevant cell line - cell type - tissue:

Upstream Regulation
Regulatory protein:
caveolin-1 (human) ( 12 ) , ID1 (human) ( 7 ) , JNK1 (human) ( 10 ) , JNK3 (mouse) ( 29 ) , LKB1 (human) ( 9 ) , RAC1 (human) ( 29 ) , TSC2 (human) ( 6 )
Putative in vivo kinases:
JNK1 (human) ( 6 , 8 , 25 ) , PKCA (human) ( 27 ) , PKCD (human) ( 2 )
Kinases, in vitro:
JNK1 (human) ( 25 ) , JNK3 (mouse) ( 29 ) , PKCA (human) ( 27 )
Treatments:
ABT-737 ( 4 ) , allyl isothiocyanate ( 5 ) , amino_acid_starvation ( 10 ) , C2-ceramide ( 8 ) , C2-DHCer ( 8 ) , ceramide ( 16 ) , cisplatin ( 15 , 20 ) , docetaxel ( 7 ) , dolastatin_10 ( 28 ) , ET18OCH3 ( 21 ) , etoposide ( 16 ) , geldanamycin ( 26 ) , heating ( 11 ) , hexamethionium ( 21 ) , hydroxyurea ( 5 ) , Hypericin ( 2 ) , light ( 2 ) , nicotine ( 21 ) , nitric_oxide ( 6 ) , okadaic_acid ( 28 ) , PD98059 ( 19 , 21 ) , photodynamic therapy ( 22 ) , plumbagin ( 14 ) , rapamycin ( 6 ) , SB202190 ( 21 ) , siRNA ( 9 ) , SP600125 ( 5 , 14 ) , staurosporine ( 19 , 21 ) , taxol ( 12 , 22 , 25 , 26 , 28 , 30 ) , testosterone ( 11 ) , vinblastine ( 28 ) , vincristine ( 28 ) , virus infection ( 3 )

Downstream Regulation
Effects of modification on Bcl-2:
activity, inhibited ( 11 , 25 ) , intracellular localization ( 22 ) , molecular association, regulation ( 5 , 6 , 8 , 10 , 15 , 21 )
Effects of modification on biological processes:
apoptosis, altered ( 9 , 17 , 24 ) , apoptosis, induced ( 2 , 5 , 11 , 25 ) , apoptosis, inhibited ( 13 , 15 , 19 , 21 , 22 ) , cell cycle regulation ( 5 ) , cell growth, altered ( 19 )
Induce interaction with:
BAX (human) ( 21 ) , BAX (mouse) ( 15 )
Inhibit interaction with:
BAX (human) ( 5 ) , beclin 1 (human) ( 6 , 8 , 10 ) , p53 (mouse) ( 15 )

References 

1

Wu MS, et al. (2019) Activation of PERK Contributes to Apoptosis and G/M Arrest by Microtubule Disruptors in Human Colorectal Carcinoma Cells . Cancers (Basel) 12
31906029   Curated Info

2

Misuth M, et al. (2017) The flashlights on a distinct role of protein kinase C δ: Phosphorylation of regulatory and catalytic domain upon oxidative stress in glioma cells. Cell Signal 34, 11-22
28237688   Curated Info

3

Klein SR, et al. (2015) C-Jun N-terminal kinases are required for oncolytic adenovirus-mediated autophagy. Oncogene 34, 5295-301
25619840   Curated Info

4

Beurlet S, et al. (2013) BCL-2 inhibition with ABT-737 prolongs survival in an NRAS/BCL-2 mouse model of AML by targeting primitive LSK and progenitor cells. Blood 122, 2864-76
23943652   Curated Info

5

Geng F, et al. (2011) Allyl isothiocyanate arrests cancer cells in mitosis, and mitotic arrest in turn leads to apoptosis via Bcl-2 protein phosphorylation. J Biol Chem 286, 32259-67
21778226   Curated Info

6

Sarkar S, et al. (2011) Complex inhibitory effects of nitric oxide on autophagy. Mol Cell 43, 19-32
21726807   Curated Info

7

Geng H, et al. (2010) ID1 enhances docetaxel cytotoxicity in prostate cancer cells through inhibition of p21. Cancer Res 70, 3239-48
20388787   Curated Info

8

Pattingre S, et al. (2009) Role of JNK1-dependent Bcl-2 phosphorylation in ceramide-induced macroautophagy. J Biol Chem 284, 2719-28
19029119   Curated Info

9

Zhong D, et al. (2008) LKB1 is necessary for Akt-mediated phosphorylation of proapoptotic proteins. Cancer Res 68, 7270-7
18794113   Curated Info

10

Wei Y, et al. (2008) JNK1-mediated phosphorylation of Bcl-2 regulates starvation-induced autophagy. Mol Cell 30, 678-88
18570871   Curated Info

11

Jia Y, et al. (2007) Signaling pathways for germ cell death in adult cynomolgus monkeys (Macaca fascicularis) induced by mild testicular hyperthermia and exogenous testosterone treatment. Biol Reprod 77, 83-92
17377139   Curated Info

12

Shajahan AN, et al. (2007) Caveolin-1 tyrosine phosphorylation enhances paclitaxel-mediated cytotoxicity. J Biol Chem 282, 5934-43
17190831   Curated Info

13

Konopleva M, et al. (2006) Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia. Cancer Cell 10, 375-88
17097560   Curated Info

14

Hsu YL, et al. (2006) Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) induces apoptosis and cell cycle arrest in A549 cells through p53 accumulation via c-Jun NH2-terminal kinase-mediated phosphorylation at serine 15 in vitro and in vivo. J Pharmacol Exp Ther 318, 484-94
16632641   Curated Info

15

Deng X, et al. (2006) Bcl2's flexible loop domain regulates p53 binding and survival. Mol Cell Biol 26, 4421-34
16738310   Curated Info

16

Lin CF, et al. (2005) Bcl-2 rescues ceramide- and etoposide-induced mitochondrial apoptosis through blockage of caspase-2 activation. J Biol Chem 280, 23758-65
15817479   Curated Info

17

Müller IM, et al. (2005) Cephalostatin 1 inactivates Bcl-2 by hyperphosphorylation independent of M-phase arrest and DNA damage. Mol Pharmacol 67, 1684-9
15703383   Curated Info

18

Chan SM, et al. (2004) Protein microarrays for multiplex analysis of signal transduction pathways. Nat Med 10, 1390-6
15558056   Curated Info

19

Jin Z, Gao F, Flagg T, Deng X (2004) Tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone promotes functional cooperation of Bcl2 and c-Myc through phosphorylation in regulating cell survival and proliferation. J Biol Chem 279, 40209-19
15210690   Curated Info

20

Kumar Biswas S, Huang J, Persaud S, Basu A (2004) Down-regulation of Bcl-2 is associated with cisplatin resistance in human small cell lung cancer H69 cells. Mol Cancer Ther 3, 327-34
15026553   Curated Info

21

Mai H, et al. (2003) A functional role for nicotine in Bcl2 phosphorylation and suppression of apoptosis. J Biol Chem 278, 1886-91
12421819   Curated Info

22

Vantieghem A, et al. (2002) Phosphorylation of Bcl-2 in G2/M phase-arrested cells following photodynamic therapy with hypericin involves a CDK1-mediated signal and delays the onset of apoptosis. J Biol Chem 277, 37718-31
12101183   Curated Info

23

Huang ST, Cidlowski JA (2002) Phosphorylation status modulates Bcl-2 function during glucocorticoid-induced apoptosis in T lymphocytes. FASEB J 16, 825-32
12039864   Curated Info

24

Thomas A, Giesler T, White E (2000) p53 mediates bcl-2 phosphorylation and apoptosis via activation of the Cdc42/JNK1 pathway. Oncogene 19, 5259-69
11077443   Curated Info

25

Yamamoto K, Ichijo H, Korsmeyer SJ (1999) BCL-2 is phosphorylated and inactivated by an ASK1/Jun N-terminal protein kinase pathway normally activated at G(2)/M. Mol Cell Biol 19, 8469-78
10567572   Curated Info

26

Basu A, Haldar S (1998) Microtubule-damaging drugs triggered bcl2 phosphorylation-requirement of phosphorylation on both serine-70 and serine-87 residues of bcl2 protein. Int J Oncol 13, 659-64
9735392   Curated Info

27

Ruvolo PP, Deng X, Carr BK, May WS (1998) A functional role for mitochondrial protein kinase Calpha in Bcl2 phosphorylation and suppression of apoptosis. J Biol Chem 273, 25436-42
9738012   Curated Info

28

Haldar S, Basu A, Croce CM (1998) Serine-70 is one of the critical sites for drug-induced Bcl2 phosphorylation in cancer cells. Cancer Res 58, 1609-15
9563469   Curated Info

29

Maundrell K, et al. (1997) Bcl-2 undergoes phosphorylation by c-Jun N-terminal kinase/stress-activated protein kinases in the presence of the constitutively active GTP-binding protein Rac1. J Biol Chem 272, 25238-42
9312139   Curated Info

30

Basu A, et al. Proteasomal degradation of human peptidyl prolyl isomerase pin1-pointing phospho Bcl2 toward dephosphorylation. Neoplasia 4, 218-27
11988841   Curated Info