Ser232
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Home > Phosphorylation Site Page: > Ser232  -  PDHA1 (human)

Site Information
NRyGMGtsVERAAAS   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 448257

In vivo Characterization
Methods used to characterize site in vivo:
immunoassay ( 3 , 11 ) , mass spectrometry ( 5 , 6 , 10 , 12 , 13 , 14 , 16 , 17 , 18 , 20 , 22 , 23 , 24 , 25 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 54 , 59 ) , phospho-antibody ( 2 , 4 , 7 , 9 , 15 , 21 ) , western blotting ( 2 , 3 , 4 , 7 , 9 , 15 , 21 )
Disease tissue studied:
brain cancer ( 15 ) , glioma ( 15 ) , breast cancer ( 3 , 24 ) , breast adenocarcinoma ( 3 ) , cervical cancer ( 40 ) , cervical adenocarcinoma ( 40 ) , HNSCC ( 7 ) , leukemia ( 28 , 46 ) , acute myelogenous leukemia ( 28 ) , acute erythroid leukemias, including erythroleukemia (M6a) and very rare pure erythroid leukemia (M6b) ( 23 ) , acute megakaryoblastic leukemia (M7) ( 23 ) , acute monoblastic leukemia (M5a) or acute monocytic leukemia (M5b) ( 23 ) , acute myeloblastic leukemia, with granulocytic maturation (M2) ( 23 ) , acute myeloblastic leukemia, without maturation (M1) ( 23 ) , chronic myelogenous leukemia ( 46 ) , liver cancer ( 21 ) , hepatocellular carcinoma, surrounding tissue ( 37 ) , lung cancer ( 9 , 16 , 24 , 32 ) , non-small cell lung cancer ( 9 , 24 ) , non-small cell lung adenocarcinoma ( 16 ) , non-small cell large cell lung carcinoma ( 9 ) , non-small cell squamous cell lung carcinoma ( 9 ) , lymphoma ( 13 ) , B cell lymphoma ( 23 ) , Burkitt's lymphoma ( 13 ) , non-Hodgkin's lymphoma ( 23 ) , follicular lymphoma ( 13 ) , mantle cell lymphoma ( 13 ) , neuroblastoma ( 22 ) , ovarian cancer ( 4 ) , pancreatic cancer ( 7 ) , pancreatic carcinoma ( 7 ) , pancreatic ductal adenocarcinoma ( 14 ) , multiple myeloma ( 23 ) , prostate cancer ( 11 , 39 )
Relevant cell line - cell type - tissue:
'muscle, skeletal' ( 30 , 41 ) , 'pancreatic, ductal'-pancreas ( 14 ) , 293 (epithelial) [AT1 (human), transfection, AT1R stable transfected HEK293] ( 34 ) , 293 (epithelial) [AT1 (human), transfection] ( 33 ) , 293E (epithelial) ( 29 ) , A431 (epithelial) ( 59 ) , A549 (pulmonary) ( 17 ) , AML-193 (monocyte) ( 23 ) , astrocyte [IDH1 (human), genetic knockin] ( 15 ) , BT-20 (breast cell) ( 24 ) , BT-549 (breast cell) ( 24 ) , Calu 6 (pulmonary) ( 24 ) , CL1-0 (pulmonary) ( 32 ) , CL1-1 (pulmonary) ( 32 ) , CL1-2 (pulmonary) ( 32 ) , CL1-5 (pulmonary) ( 32 ) , CMK (megakaryoblast) ( 23 ) , COS (fibroblast) ( 51 ) , CTS (myeloid) ( 23 ) , DOHH2 ('B lymphocyte, precursor') ( 23 ) , DT14/06T (breast cell) ( 3 ) , EBC-1 (squamous) ( 9 ) , Flp-In T-Rex-293 (epithelial) [PRKD1 (human), genetic knockin] ( 25 ) , Flp-In T-Rex-293 (epithelial) ( 25 ) , GM00130 (B lymphocyte) ( 36 ) , H2009 (pulmonary) ( 24 ) , H2077 (pulmonary) ( 24 ) , H2887 (pulmonary) ( 24 ) , H322M (pulmonary) ( 24 ) , HCC1359 (pulmonary) ( 24 ) , HCC1937 (breast cell) ( 24 ) , HCC2279 (pulmonary) ( 24 ) , HCC366 (pulmonary) ( 24 ) , HCC4006 (pulmonary) ( 24 ) , HCC78 (pulmonary) ( 24 ) , HCC827 (pulmonary) ( 24 ) , HEK293T (epithelial) ( 10 ) , HEL (erythroid) ( 23 ) , HeLa (cervical) ( 5 , 9 , 12 , 20 , 42 , 43 , 47 , 48 , 52 , 54 ) , HeLa S3 (cervical) ( 40 , 45 ) , HeLa_Meta (cervical) ( 35 ) , HeLa_Pro (cervical) ( 35 ) , HeLa_Telo (cervical) ( 35 ) , hepatocyte-liver ( 37 ) , HepG2 (hepatic) ( 21 ) , HOP62 (pulmonary) ( 24 ) , HUES-9 ('stem, embryonic') ( 31 ) , JEKO-1 (B lymphocyte) ( 13 ) , Jurkat (T lymphocyte) ( 18 , 44 , 49 ) , K562 (erythroid) ( 20 , 46 ) , Kasumi-1 (myeloid) ( 23 ) , KG-1 (myeloid) ( 23 , 28 ) , LCLC-103H (pulmonary) ( 24 ) , leukocyte-blood ( 38 ) , LNCaP (prostate cell) ( 39 ) , LOU-NH91 (squamous) ( 24 ) , lung ( 16 ) , MCF-7 (breast cell) ( 24 ) , MDA-MB-231 (breast cell) ( 24 ) , MDA-MB-468 (breast cell) ( 24 ) , MIA PaCa-2 (pancreatic) ( 7 ) , MTH52C (breast cell) ( 3 ) , MTH53A (breast cell) ( 3 ) , MV4-11 (macrophage) ( 23 ) , myoblast ( 2 ) , NB10 (neural crest) ( 22 ) , NCEB-1 (B lymphocyte) ( 13 ) , NCI-H1395 (pulmonary) ( 24 ) , NCI-H1568 (pulmonary) ( 24 ) , NCI-H157 (pulmonary) ( 24 ) , NCI-H1648 (pulmonary) ( 24 ) , NCI-H1666 (pulmonary) ( 24 ) , NCI-H2030 (pulmonary) ( 24 ) , NCI-H2172 (pulmonary) ( 24 ) , NCI-H322 (pulmonary) ( 24 ) , NCI-H460 (pulmonary) ( 9 , 24 , 42 ) , NCI-H520 (squamous) ( 24 ) , NCI-H647 (pulmonary) ( 24 ) , NPC (neural crest) ( 22 ) , OCI-ly1 (B lymphocyte) ( 13 ) , OPM-2 (plasma cell) ( 23 ) , P31/FUJ (erythroid) ( 23 ) , PC3 (prostate cell) ( 11 ) , PC9 (pulmonary) ( 24 ) , platelet-blood ( 50 ) , Raji (B lymphocyte) ( 13 ) , REC-1 (B lymphocyte) ( 13 ) , RL ('B lymphocyte, precursor') ( 23 ) , RPMI-8266 (plasma cell) ( 23 ) , SKOV-3 (ovarian) ( 4 ) , SU-DHL-4 (B lymphocyte) ( 13 ) , SU-DHL-6 (B lymphocyte) ( 23 ) , Su.86.86 (pancreatic) ( 7 ) , U266 (plasma cell) ( 23 ) , ZMTH3 (breast cell) ( 3 )

Upstream Regulation
Regulatory protein:
HIF1A (human) ( 7 ) , PDHK1 (human) ( 7 ) , PDP1 (human) ( 7 ) , STAU (human) ( 2 )
Kinases, in vitro:
PDHK1 (human) ( 53 , 55 , 57 , 58 ) , PDHK2 (human) ( 57 ) , PDK1 (human) ( 56 )
Phosphatases, in vitro:
PDP1 (human) ( 58 )
Treatments:
CoCL2 ( 21 ) , DCA ( 3 ) , desferoxamine ( 21 ) , dicoumarol ( 4 ) , DMOG ( 21 ) , EGF ( 5 ) , hypoxia ( 7 , 21 ) , JX06 ( 9 ) , metastatic potential ( 32 ) , MG132 ( 35 ) , nocodazole ( 40 ) , oleic_acid ( 6 ) , VER-246608 ( 11 )

Downstream Regulation
Effects of modification on PDHA1:
enzymatic activity, inhibited ( 11 , 57 , 58 )
Effects of modification on biological processes:
cell growth, induced ( 7 )

Disease / Diagnostics Relevance
Relevant diseases:
HNSCC ( 7 )

References 

1

Zhuang Y, et al. (2019) The novel function of tumor protein D54 in regulating pyruvate dehydrogenase and metformin cytotoxicity in breast cancer. Cancer Metab 7, 1
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2

Lucas BA, et al. (2018) Evidence for convergent evolution of SINE-directed Staufen-mediated mRNA decay. Proc Natl Acad Sci U S A 115, 968-973
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3

Harting TP, et al. (2017) Dichloroacetate affects proliferation but not apoptosis in canine mammary cell lines. PLoS One 12, e0178744
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4

Zhang W, et al. (2017) Dicumarol inhibits PDK1 and targets multiple malignant behaviors of ovarian cancer cells. PLoS One 12, e0179672
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5

Huang H, et al. (2016) Simultaneous Enrichment of Cysteine-containing Peptides and Phosphopeptides Using a Cysteine-specific Phosphonate Adaptable Tag (CysPAT) in Combination with titanium dioxide (TiO2) Chromatography. Mol Cell Proteomics 15, 3282-3296
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6

Zhao H, Pflug BR, Lai X, Wang M (2016) Pyruvate dehydrogenase alpha 1 as a target of omega-3 polyunsaturated fatty acids in human prostate cancer through a global phosphoproteomic analysis. Proteomics 16, 2419-31
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7

Golias T, et al. (2016) Hypoxic repression of pyruvate dehydrogenase activity is necessary for metabolic reprogramming and growth of model tumours. Sci Rep 6, 31146
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8

Malec V, Coulson JM, Urbé S, Clague MJ (2015) Combined Analyses of the VHL and Hypoxia Signaling Axes in an Isogenic Pairing of Renal Clear Cell Carcinoma Cells. J Proteome Res 14, 5263-72
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9

Sun W, et al. (2015) JX06 Selectively Inhibits Pyruvate Dehydrogenase Kinase PDK1 by a Covalent Cysteine Modification. Cancer Res 75, 4923-36
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10

Franchin C, et al. (2015) Quantitative analysis of a phosphoproteome readily altered by the protein kinase CK2 inhibitor quinalizarin in HEK-293T cells. Biochim Biophys Acta 1854, 609-23
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11

Moore JD, et al. (2014) VER-246608, a novel pan-isoform ATP competitive inhibitor of pyruvate dehydrogenase kinase, disrupts Warburg metabolism and induces context-dependent cytostasis in cancer cells. Oncotarget 5, 12862-76
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12

Sharma K, et al. (2014) Ultradeep human phosphoproteome reveals a distinct regulatory nature of Tyr and Ser/Thr-based signaling. Cell Rep 8, 1583-94
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13

Rolland D, et al. (2014) Global phosphoproteomic profiling reveals distinct signatures in B-cell non-Hodgkin lymphomas. Am J Pathol 184, 1331-42
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14

Britton D, et al. (2014) Quantification of pancreatic cancer proteome and phosphorylome: indicates molecular events likely contributing to cancer and activity of drug targets. PLoS One 9, e90948
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15

Izquierdo-Garcia JL, et al. (2014) Glioma Cells with the IDH1 Mutation Modulate Metabolic Fractional Flux through Pyruvate Carboxylase. PLoS One 9, e108289
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16

Schweppe DK, Rigas JR, Gerber SA (2013) Quantitative phosphoproteomic profiling of human non-small cell lung cancer tumors. J Proteomics 91, 286-96
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17

Kim JY, et al. (2013) Dissection of TBK1 signaling via phosphoproteomics in lung cancer cells. Proc Natl Acad Sci U S A 110, 12414-9
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18

Mertins P, et al. (2013) Integrated proteomic analysis of post-translational modifications by serial enrichment. Nat Methods 10, 634-7
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19

Shiromizu T, et al. (2013) Identification of missing proteins in the neXtProt database and unregistered phosphopeptides in the PhosphoSitePlus database as part of the Chromosome-centric Human Proteome Project. J Proteome Res 12, 2414-21
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20

Zhou H, et al. (2013) Toward a comprehensive characterization of a human cancer cell phosphoproteome. J Proteome Res 12, 260-71
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21

Borcar A, Menze MA, Toner M, Hand SC (2013) Metabolic preconditioning of mammalian cells: mimetic agents for hypoxia lack fidelity in promoting phosphorylation of pyruvate dehydrogenase. Cell Tissue Res 351, 99-106
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22

DeNardo BD, et al. (2013) Quantitative phosphoproteomic analysis identifies activation of the RET and IGF-1R/IR signaling pathways in neuroblastoma. PLoS One 8, e82513
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23

Casado P, et al. (2013) Phosphoproteomics data classify hematological cancer cell lines according to tumor type and sensitivity to kinase inhibitors. Genome Biol 14, R37
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24

Klammer M, et al. (2012) Phosphosignature predicts dasatinib response in non-small cell lung cancer. Mol Cell Proteomics 11, 651-68
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25

Franz-Wachtel M, et al. (2012) Global detection of protein kinase D-dependent phosphorylation events in nocodazole-treated human cells. Mol Cell Proteomics 11, 160-70
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26

Beli P, et al. (2012) Proteomic Investigations Reveal a Role for RNA Processing Factor THRAP3 in the DNA Damage Response. Mol Cell 46, 212-25
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27

Xue X, et al. (2012) Mitaplatin increases sensitivity of tumor cells to Cisplatin by inducing mitochondrial dysfunction. Mol Pharm 9, 634-44
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28

Weber C, Schreiber TB, Daub H (2012) Dual phosphoproteomics and chemical proteomics analysis of erlotinib and gefitinib interference in acute myeloid leukemia cells. J Proteomics 75, 1343-56
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29

Hsu PP, et al. (2011) The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling. Science 332, 1317-22
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30

Zhao X, et al. (2011) Phosphoproteome analysis of functional mitochondria isolated from resting human muscle reveals extensive phosphorylation of inner membrane protein complexes and enzymes. Mol Cell Proteomics 10, M110.000299
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31

Rigbolt KT, et al. (2011) System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal 4, rs3
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32

Wang YT, et al. (2010) An informatics-assisted label-free quantitation strategy that depicts phosphoproteomic profiles in lung cancer cell invasion. J Proteome Res 9, 5582-97
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33

Xiao K, et al. (2010) Global phosphorylation analysis of beta-arrestin-mediated signaling downstream of a seven transmembrane receptor (7TMR). Proc Natl Acad Sci U S A 107, 15299-304
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34

Christensen GL, et al. (2010) Quantitative phosphoproteomics dissection of seven-transmembrane receptor signaling using full and biased agonists. Mol Cell Proteomics 9, 1540-53
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35

Dulla K, et al. (2010) Quantitative site-specific phosphorylation dynamics of human protein kinases during mitotic progression. Mol Cell Proteomics 9, 1167-81
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36

Bennetzen MV, et al. (2010) Site-specific phosphorylation dynamics of the nuclear proteome during the DNA damage response. Mol Cell Proteomics 9, 1314-23
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37

Han G, et al. (2010) Phosphoproteome analysis of human liver tissue by long-gradient nanoflow LC coupled with multiple stage MS analysis. Electrophoresis 31, 1080-9
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38

Raijmakers R, et al. (2010) Exploring the human leukocyte phosphoproteome using a microfluidic reversed-phase-TiO2-reversed-phase high-performance liquid chromatography phosphochip coupled to a quadrupole time-of-flight mass spectrometer. Anal Chem 82, 824-32
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39

Chen L, Giorgianni F, Beranova-Giorgianni S (2010) Characterization of the phosphoproteome in LNCaP prostate cancer cells by in-gel isoelectric focusing and tandem mass spectrometry. J Proteome Res 9, 174-8
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40

Olsen JV, et al. (2010) Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal 3, ra3
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41

Højlund K, et al. (2009) In vivo phosphoproteome of human skeletal muscle revealed by phosphopeptide enrichment and HPLC-ESI-MS/MS. J Proteome Res 8, 4954-65
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42

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43

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44

Mayya V, et al. (2009) Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal 2, ra46
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45

Daub H, et al. (2008) Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell 31, 438-48
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46

Stokes M (2008) CST Curation Set: 4391; Year: 2008; Biosample/Treatment: cell line, K562/untreated; Disease: chronic myelogenous leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

47

McNulty DE, Annan RS (2008) Hydrophilic interaction chromatography reduces the complexity of the phosphoproteome and improves global phosphopeptide isolation and detection. Mol Cell Proteomics 7, 971-80
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48

Cantin GT, et al. (2008) Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis. J Proteome Res 7, 1346-51
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49

Stokes M (2008) CST Curation Set: 3884; Year: 2008; Biosample/Treatment: cell line, Jurkat/pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

50

Zahedi RP, et al. (2008) Phosphoproteome of resting human platelets. J Proteome Res 7, 526-34
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51

Wang Y, et al. (2007) Profiling signaling polarity in chemotactic cells. Proc Natl Acad Sci U S A 104, 8328-33
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52

Beausoleil SA, et al. (2006) A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nat Biotechnol 24, 1285-92
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53

Korotchkina LG, Sidhu S, Patel MS (2006) Characterization of testis-specific isoenzyme of human pyruvate dehydrogenase. J Biol Chem 281, 9688-96
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54

Beausoleil SA, et al. (2004) Large-scale characterization of HeLa cell nuclear phosphoproteins. Proc Natl Acad Sci U S A 101, 12130-5
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55

Korotchkina LG, Patel MS (2001) Site specificity of four pyruvate dehydrogenase kinase isoenzymes toward the three phosphorylation sites of human pyruvate dehydrogenase. J Biol Chem 276, 37223-9
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56

Kolobova E, Tuganova A, Boulatnikov I, Popov KM (2001) Regulation of pyruvate dehydrogenase activity through phosphorylation at multiple sites. Biochem J 358, 69-77
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57

Korotchkina LG, Patel MS (2001) Probing the mechanism of inactivation of human pyruvate dehydrogenase by phosphorylation of three sites. J Biol Chem 276, 5731-8
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58

Korotchkina LG, Patel MS (1995) Mutagenesis studies of the phosphorylation sites of recombinant human pyruvate dehydrogenase. Site-specific regulation. J Biol Chem 270, 14297-304
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59

MS This site is one of 509 sites observed by D. Stover et al using MS/FTMS of peptides from lysates of A431 cells grown either in vitro or as xenografts in BALB/c nu/nu mice. These sites were previously unpublished until now (July 27 2006). 66 sites were previously published in: Stover DR, et al. Differential phosphoprofiles of EGF and EGFR kinase inhibitor-treated human tumor cells and mouse xenografts Clin Proteomics 2004 Mar 01; 1(1): 69-80.
Curated Info