Tyr307
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Home > Phosphorylation Site Page: > Tyr307  -  PPP2CA (human)

Site Information
VTRRTPDyFL_____   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 448571

In vivo Characterization
Methods used to characterize site in vivo:
immunoassay ( 21 ) , immunoprecipitation ( 1 , 4 , 8 , 24 , 26 , 28 ) , modification-specific antibody ( 7 , 31 ) , mutation of modification site ( 31 , 32 , 36 , 37 ) , phospho-antibody ( 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 10 , 16 , 21 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 33 , 34 ) , western blotting ( 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 16 , 24 , 25 , 26 , 27 , 28 , 29 , 31 , 33 , 34 )
Disease tissue studied:
breast cancer ( 6 , 24 , 29 ) , cervical cancer ( 26 ) , cervical squamous cell carcinoma ( 26 ) , colorectal cancer ( 10 ) , leukemia ( 2 , 5 , 16 ) , acute myelogenous leukemia ( 2 ) , acute erythroid leukemias, including erythroleukemia (M6a) and very rare pure erythroid leukemia (M6b) ( 16 ) , chronic lymphocytic leukemia ( 5 ) , lymphoma ( 3 , 28 ) , neuroblastoma ( 4 , 32 ) , multiple myeloma ( 21 )
Relevant cell line - cell type - tissue:
'neuron, cortical' ( 4 ) , 293 (epithelial) ( 1 , 8 ) , 32D (myeloid) [IRS1 (mouse)] ( 35 ) , 3T3 (fibroblast) ( 32 ) , 661W ( 27 ) , B lymphocyte ( 5 ) , BaF3 ('B lymphocyte, precursor') ( 2 ) , brain ( 30 ) , BT-474 (breast cell) ( 6 , 24 ) , colon ( 10 ) , COS (fibroblast) ( 36 ) , COS7 (fibroblast) ( 31 ) , EBV-LCL (lymphoblast) ( 8 , 21 ) , heart ( 25 ) , HeLa (cervical) ( 31 ) , HL-7702 (hepatic) ( 7 ) , KB (squamous) ( 26 ) , MCF-7 (breast cell) ( 6 ) , MCF12A (epithelial) ( 24 ) , MDA-MB-231 (breast cell) ( 6 , 29 ) , MDCK (epithelial) ( 33 ) , MV4-11 (macrophage) ( 2 ) , Neuro-2a (neuron) ( 32 ) , S.cerevisiae [PPP2CA (human), transfection] ( 37 ) , SKBr3 (breast cell) ( 6 , 24 ) , SKNSH (neural crest) ( 4 ) , T lymphocyte-lymph node ( 34 ) , TF-1 (erythroid) ( 16 ) , U-937 (myeloid) ( 3 , 28 )

Upstream Regulation
Regulatory protein:
AMPKA1 (human) ( 29 ) , G-alpha 12 (mouse) ( 33 ) , GBA (human) ( 4 ) , SETBP1 (human) ( 16 )
Putative in vivo kinases:
Src (human) ( 26 , 27 )
Kinases, in vitro:
EGFR (human) ( 38 ) , INSR (human) ( 38 ) , Lck (human) ( 38 ) , Src (human) ( 26 , 38 )
Putative upstream phosphatases:
PTPRA (human) ( 15 )
Treatments:
acadesine ( 29 ) , adiponectin ( 29 ) , blood pressure ( 25 ) , BMAA ( 11 ) , C2-ceramide ( 4 ) , cell_adhesion ( 28 ) , ceramide ( 8 ) , colforsin ( 9 ) , dasatinib ( 5 ) , ethanol ( 34 ) , fingolimod ( 2 ) , geldanamycin ( 5 ) , growth_factor_withdrawal ( 27 ) , H2O2 ( 27 ) , IL-1b ( 26 ) , imatinib ( 35 ) , injury ( 34 ) , microcystin-LR ( 1 , 7 ) , NAC ( 27 ) , okadaic_acid ( 28 , 29 ) , PP2 ( 5 , 27 ) , saracatinib ( 5 ) , vanadate ( 5 , 26 )

Downstream Regulation
Effects of modification on PPP2CA:
enzymatic activity, inhibited ( 4 , 5 , 8 , 21 , 24 , 26 , 27 , 29 , 33 , 37 ) , intracellular localization ( 29 ) , methylation ( 23 ) , molecular association, regulation ( 5 , 23 , 32 , 36 )
Effects of modification on biological processes:
apoptosis, altered ( 24 ) , autophagy, inhibited ( 4 ) , cell growth, altered ( 37 ) , cytoskeletal reorganization ( 32 ) , translation, induced ( 4 )
Induce interaction with:
ASH2L (human) ( 5 ) , LCMT1 (human) ( 23 )
Inhibit interaction with:
JAK2 (human) ( 36 ) , PPP2R2A (mouse) ( 32 ) , PPP2R3A (mouse) ( 32 )

Disease / Diagnostics Relevance
Relevant diseases:
Alzheimer's disease ( 30 ) , colorectal cancer ( 10 )

References 

1

Huang P, et al. (2017) HEK293 cells exposed to microcystin-LR show reduced protein phosphatase 2A activity and more stable cytoskeletal structure when overexpressing α4 protein. Environ Toxicol 32, 255-264
26784437   Curated Info

2

Smith AM, et al. (2016) Activation of protein phosphatase 2A in FLT3+ acute myeloid leukemia cells enhances the cytotoxicity of FLT3 tyrosine kinase inhibitors. Oncotarget 7, 47465-47478
27329844   Curated Info

3

Kobayashi Y, et al. (2016) Protein tyrosine phosphatase PTP-RR regulates corticosteroid sensitivity. Respir Res 17, 30
27013170   Curated Info

4

Du TT, et al. (2015) GBA deficiency promotes SNCA/α-synuclein accumulation through autophagic inhibition by inactivated PPP2A. Autophagy 11, 1803-20
26378614   Curated Info

5

Zonta F, et al. (2015) Lyn sustains oncogenic signaling in chronic lymphocytic leukemia by strengthening SET-mediated inhibition of PP2A. Blood 125, 3747-55
25931585   Curated Info

6

Rincón R, et al. (2015) PP2A inhibition determines poor outcome and doxorubicin resistance in early breast cancer and its activation shows promising therapeutic effects. Oncotarget 6, 4299-314
25726524   Curated Info

7

Sun Y, et al. (2014) Microcystin-LR induces protein phosphatase 2A alteration in a human liver cell line. Environ Toxicol 29, 1236-44
23436320   Curated Info

8

Preuss KD, et al. (2014) Inactivation of protein-phosphatase 2A causing hyperphosphorylation of autoantigenic paraprotein targets in MGUS/MM is due to an exchange of its regulatory subunits. Int J Cancer 135, 2046-53
24676687   Curated Info

9

Cristóbal I, et al. (2014) Hyperphosphorylation of PP2A in colorectal cancer and the potential therapeutic value showed by its forskolin-induced dephosphorylation and activation. Biochim Biophys Acta 1842, 1823-9
24997451   Curated Info

10

Cristóbal I, et al. (2014) Phosphorylated protein phosphatase 2A determines poor outcome in patients with metastatic colorectal cancer. Br J Cancer 111, 756-62
25003662   Curated Info

11

Arif M, et al. (2014) Tau pathology involves protein phosphatase 2A in Parkinsonism-dementia of Guam. Proc Natl Acad Sci U S A 111, 1144-9
24395787   Curated Info

12

Nardi F, et al. (2014) Enhanced Insulin Sensitivity Associated with Provision of Mono and Polyunsaturated Fatty Acids in Skeletal Muscle Cells Involves Counter Modulation of PP2A. PLoS One 9, e92255
24632852   Curated Info

13

Oaks JJ, et al. (2013) Antagonistic activities of the immunomodulator and PP2A-activating drug FTY720 (Fingolimod, Gilenya) in Jak2-driven hematologic malignancies. Blood 122, 1923-34
23926298   Curated Info

14

Cao Z, et al. (2013) X-linked Inhibitor of Apoptosis Protein (XIAP) Regulation of Cyclin D1 Protein Expression and Cancer Cell Anchorage-independent Growth via Its E3 Ligase-mediated Protein Phosphatase 2A/c-Jun Axis. J Biol Chem 288, 20238-47
23720779   Curated Info

15

Luo Y, et al. (2013) PTPA activates protein phosphatase-2A through reducing its phosphorylation at tyrosine-307 with upregulation of protein tyrosine phosphatase 1B. Biochim Biophys Acta 1833, 1235-43
23428800   Curated Info

16

Piazza R, et al. (2013) Recurrent SETBP1 mutations in atypical chronic myeloid leukemia. Nat Genet 45, 18-24
23222956   Curated Info

17

Samuel GH, et al. (2012) Acid sphingomyelinase deficiency contributes to resistance of scleroderma fibroblasts to Fas-mediated apoptosis. J Dermatol Sci 67, 166-72
22771321   Curated Info

18

Torrent L, Ferrer I (2012) PP2A and Alzheimer disease. Curr Alzheimer Res 9, 248-56
22299660   Curated Info

19

Woo CW, Kutzler L, Kimball SR, Tabas I (2012) Toll-like receptor activation suppresses ER stress factor CHOP and translation inhibition through activation of eIF2B. Nat Cell Biol 14, 192-200
22231169   Curated Info

20

Irie A, Harada K, Araki N, Nishimura Y (2012) Phosphorylation of SET Protein at Ser171 by Protein Kinase D2 Diminishes Its Inhibitory Effect on Protein Phosphatase 2A. PLoS One 7, e51242
23251465   Curated Info

21

Preuss KD, et al. (2011) Hyperphosphorylation of autoantigenic targets of paraproteins is due to inactivation of PP2A. Blood 118, 3340-6
21791414   Curated Info

22

Yao XQ, et al. (2011) Glycogen synthase kinase-3β regulates Tyr307 phosphorylation of protein phosphatase-2A via protein tyrosine phosphatase 1B but not Src. Biochem J 437, 335-44
21554241   Curated Info

23

Stanevich V, et al. (2011) The structural basis for tight control of PP2A methylation and function by LCMT-1. Mol Cell 41, 331-42
21292165   Curated Info

24

Wong LL, Zhang D, Chang CF, Koay ES (2010) Silencing of the PP2A catalytic subunit causes HER-2/neu positive breast cancer cells to undergo apoptosis. Exp Cell Res 316, 3387-96
20558158   Curated Info

25

Cheng G, et al. (2010) Basis for MAP4 Dephosphorylation-related Microtubule Network Densification in Pressure Overload Cardiac Hypertrophy. J Biol Chem 285, 38125-40
20889984   Curated Info

26

Barisic S, Schmidt C, Walczak H, Kulms D (2010) Tyrosine phosphatase inhibition triggers sustained canonical serine-dependent NFkappaB activation via Src-dependent blockade of PP2A. Biochem Pharmacol 80, 439-47
20450893   Curated Info

27

Finnegan S, Mackey AM, Cotter TG (2010) A stress survival response in retinal cells mediated through inhibition of the serine/threonine phosphatase PP2A. Eur J Neurosci 32, 322-34
20636478   Curated Info

28

De Toni-Costes F, et al. (2010) A New alpha5beta1 integrin-dependent survival pathway through GSK3beta activation in leukemic cells. PLoS One 5, e9807
20352103   Curated Info

29

Kim KY, et al. (2009) Adiponectin-activated AMPK stimulates dephosphorylation of AKT through protein phosphatase 2A activation. Cancer Res 69, 4018-26
19366811   Curated Info

30

Liu R, et al. (2008) Phosphorylated PP2A (tyrosine 307) is associated with Alzheimer neurofibrillary pathology. J Cell Mol Med 12, 241-57
18208556   Curated Info

31

Longin S, et al. (2007) Selection of protein phosphatase 2A regulatory subunits is mediated by the C terminus of the catalytic Subunit. J Biol Chem 282, 26971-80
17635907   Curated Info

32

Nunbhakdi-Craig V, et al. (2007) Expression of protein phosphatase 2A mutants and silencing of the regulatory B alpha subunit induce a selective loss of acetylated and detyrosinated microtubules. J Neurochem 101, 959-71
17394530   Curated Info

33

Zhu D, et al. (2007) Domains necessary for Galpha12 binding and stimulation of protein phosphatase-2A (PP2A): Is Galpha12 a novel regulatory subunit of PP2A? Mol Pharmacol 71, 1268-76
17303700   Curated Info

34

Li X, Schwacha MG, Chaudry IH, Choudhry MA (2006) A role of PP1/PP2A in mesenteric lymph node T cell suppression in a two-hit rodent model of alcohol intoxication and injury. J Leukoc Biol 79, 453-62
16387841   Curated Info

35

Neviani P, et al. (2005) The tumor suppressor PP2A is functionally inactivated in blast crisis CML through the inhibitory activity of the BCR/ABL-regulated SET protein. Cancer Cell 8, 355-68
16286244   Curated Info

36

Yokoyama N, Reich NC, Miller WT (2003) Determinants for the interaction between Janus kinase 2 and protein phosphatase 2A. Arch Biochem Biophys 417, 87-95
12921784   Curated Info

37

Evans DR, Hemmings BA (2000) Important role for phylogenetically invariant PP2Acalpha active site and C-terminal residues revealed by mutational analysis in Saccharomyces cerevisiae. Genetics 156, 21-9
10978272   Curated Info

38

Chen J, Martin BL, Brautigan DL (1992) Regulation of protein serine-threonine phosphatase type-2A by tyrosine phosphorylation. Science 257, 1261-4
1325671   Curated Info