Thr410
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Home > Phosphorylation Site Page: > Thr410  -  PKCZ (human)

Site Information
GPGDtTstFCGtPNy   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447510
Available spectra:  1 CST

In vivo Characterization
Methods used to characterize site in vivo:
[32P] bio-synthetic labeling ( 18 , 39 ) , immunoassay ( 7 ) , immunoprecipitation ( 6 , 17 ) , mass spectrometry ( 1 , 2 , 3 , 9 , 11 , 12 , 13 , 14 , 15 , 16 , 19 ) , mutation of modification site ( 6 , 10 , 21 , 27 , 32 , 34 , 39 ) , peptide sequencing ( 18 ) , phospho-antibody ( 4 , 5 , 6 , 7 , 8 , 17 , 20 , 21 , 22 , 23 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ) , western blotting ( 4 , 5 , 6 , 7 , 8 , 17 , 20 , 21 , 23 , 25 , 26 , 27 , 29 , 31 , 34 , 35 , 37 , 38 )
Disease tissue studied:
breast cancer ( 17 , 21 , 32 ) , cervical cancer ( 20 , 21 , 27 ) , cervical adenocarcinoma ( 20 , 21 , 27 ) , gestational cancer ( 26 ) , gestational trophoblastic choriocarcinoma ( 26 ) , leukemia ( 4 ) , T cell leukemia ( 4 ) , lung cancer ( 1 , 8 , 9 , 11 , 12 , 13 , 14 , 15 , 16 , 20 , 27 ) , non-small cell lung cancer ( 1 , 11 , 13 , 14 , 15 , 16 ) , non-small cell lung adenocarcinoma ( 1 ) , cancer, squamous cell carcinoma ( 7 )
Relevant cell line - cell type - tissue:
'muscle, skeletal' ( 28 , 31 ) , 'muscle, smooth' ( 22 ) , 293 (epithelial) ( 6 , 18 , 33 , 34 , 38 ) , 3T3-L1 (fibroblast) ( 27 ) , A549 (pulmonary) ( 8 , 20 , 27 ) , aorta ( 20 ) , astrocyte-'brain, striatum' ( 37 ) , BAEC (endothelial) ( 20 , 27 ) , Cal-12T (pulmonary) ( 1 ) , CCRF-CEM (T lymphocyte) ( 4 ) , CHO (fibroblast) [EphB1 (human), transfection] ( 39 ) , COS (fibroblast) [EGFR (human), transfection] ( 10 ) , COS (fibroblast) ( 30 , 32 ) , endothelial-aorta ( 29 ) , FaDu (squamous) ( 7 ) , HCC44 (pulmonary) ( 1 ) , HeLa S3 (cervical) ( 19 , 20 , 21 , 27 ) , HL60 (myeloid) ( 36 ) , HN31 ( 7 ) , HN5 (squamous) ( 7 ) , Hs 578T (breast cell) ( 30 ) , HUVEC (endothelial) ( 20 , 21 ) , JAR (placental) ( 26 ) , lung ( 1 , 9 , 11 , 12 , 13 , 14 , 15 , 16 ) , MCF-7 (breast cell) ( 17 , 32 ) , MDA-MB-468 (breast cell) ( 21 , 30 ) , myocyte-heart ( 23 ) , NCI-H1437 (pulmonary) ( 1 ) , NCI-H1666 (pulmonary) ( 1 ) , NCI-H2405 (pulmonary) ( 1 ) , neutrophil ( 35 ) , OSC-19 (intestinal) ( 7 ) , platelet ( 5 ) , retina ( 27 ) , SCC61 (squamous) ( 7 ) , SF9 ( 25 ) , THP1 (myeloid) ( 33 ) , UMSCC1 (squamous) ( 7 ) , vascular smooth muscle cell ('muscle, smooth') ( 27 )

Upstream Regulation
Regulatory protein:
EGFR (human) ( 10 ) , HERC1 (human) ( 4 ) , mTOR (human) ( 4 ) , NUMB (mouse) ( 6 ) , PIK3C2B (human) ( 4 ) , PPP1CC (human) ( 5 ) , TNF-R1 (human) ( 23 ) , TNF-R2 (human) ( 23 )
Putative in vivo kinases:
PDK1 (mouse) ( 39 )
Kinases, in vitro:
PDK1 (human) ( 25 , 34 ) , PDK1 (mouse) ( 39 )
Treatments:
alprostadil ( 5 ) , angiotensin_2 ( 22 ) , anti-TNFR1 ( 23 ) , anti-TNFR2 ( 23 ) , arcyriarubin_A ( 27 ) , aspirin ( 5 ) , BDNF ( 6 ) , carbachol ( 37 ) , EGF ( 10 ) , estradiol ( 32 ) , ethanol ( 37 ) , exercise ( 31 ) , faslodex ( 32 ) , Go_6983 ( 27 ) , H-89 ( 27 ) , IGF-1 ( 17 ) , insulin ( 28 , 39 ) , K252a ( 6 ) , KT5823 ( 27 ) , laminar flow ( 29 ) , losartan ( 22 ) , LY294002 ( 26 , 36 ) , MAFP ( 23 ) , major_basic_protein ( 35 ) , okadaic_acid ( 4 , 5 ) , ONOO(-) ( 21 , 27 ) , PAR4-activating_peptide ( 5 ) , PD123319 ( 22 ) , phorbol_ester ( 38 ) , PKC-zeta_inhibitor ( 21 ) , salicylate ( 38 ) , SC-57101 ( 5 ) , simvastatin ( 20 ) , Sin-1 ( 21 ) , TNF ( 23 , 34 ) , trichostatin_A ( 26 ) , wortmannin ( 26 , 35 )

Downstream Regulation
Effects of modification on PKCZ:
enzymatic activity, induced ( 7 , 10 , 22 , 34 , 36 , 39 ) , molecular association, regulation ( 28 , 32 ) , protein conformation ( 25 )
Effects of modification on biological processes:
cytoskeletal reorganization ( 24 )
Induce interaction with:
MYO1C (mouse) ( 24 ) , TNNI1 (mouse) ( 24 ) , TNNT1 (mouse) ( 24 ) , TPM1 (rat) ( 24 ) , desmin (rat) ( 24 )

Disease / Diagnostics Relevance
Relevant diseases:
HNSCC ( 7 )

References 

1

Rikova K, Hall B (2013) CST Curation Set: 20741, 21168, 30173, 30174, 30175; Year: 2013; Biosample/Treatment: cell line, H1666, CAL-12T, H2405, HCC44, H1437; Disease: -; TMT: Y; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY, p[ST], RXXp[ST], pSQ, p[ST]QG, LXRXXp[ST], p[ST]P
Curated Info

2

Stokes MP, et al. (2012) PTMScan Direct: Identification and Quantification of Peptides from Critical Signaling Proteins by Immunoaffinity Enrichment Coupled with LC-MS/MS. Mol Cell Proteomics 11, 187-201
22322096   Curated Info

3

Rikova K (2011) CST Curation Set: 13128; Year: 2011; Biosample/Treatment: cell line, MGH-6/unknown; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

4

Diouf B, et al. (2011) Somatic deletions of genes regulating MSH2 protein stability cause DNA mismatch repair deficiency and drug resistance in human leukemia cells. Nat Med 17, 1298-303
21946537   Curated Info

5

Mayanglambam A, Bhavanasi D, Vijayan KV, Kunapuli SP (2011) Differential dephosphorylation of the protein kinase C-zeta (PKCζ) in an integrin αIIbβ3-dependent manner in platelets. Biochem Pharmacol 82, 505-13
21645497   Curated Info

6

Zhou P, et al. (2011) Numb links extracellular cues to intracellular polarity machinery to promote chemotaxis. Dev Cell 20, 610-22
21571219   Curated Info

7

Frederick MJ, et al. (2011) Phosphoproteomic analysis of signaling pathways in head and neck squamous cell carcinoma patient samples. Am J Pathol 178, 548-71
21281788   Curated Info

8

Leverence JT, Medhora M, Konduri GG, Sampath V (2011) Lipopolysaccharide-induced cytokine expression in alveolar epithelial cells: role of PKCζ-mediated p47phox phosphorylation. Chem Biol Interact 189, 72-81
20920494   Curated Info

9

Rikova K (2010) CST Curation Set: 9768; Year: 2010; Biosample/Treatment: tissue, lung/untreated; Disease: lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

10

Valkova C, et al. (2010) Activation by tyrosine phosphorylation as a prerequisite for protein kinase Czeta to mediate epidermal growth factor receptor signaling to ERK. Mol Cancer Res 8, 783-97
20407013   Curated Info

11

Rikova K (2010) CST Curation Set: 9470; Year: 2010; Biosample/Treatment: tissue, /untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

12

Rikova K (2010) CST Curation Set: 9467; Year: 2010; Biosample/Treatment: tissue, lung/untreated; Disease: lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

13

Rikova K (2010) CST Curation Set: 9461; Year: 2010; Biosample/Treatment: tissue, lung/untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

14

Rikova K (2010) CST Curation Set: 9456; Year: 2010; Biosample/Treatment: tissue, lung/untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

15

Rikova K (2010) CST Curation Set: 9457; Year: 2010; Biosample/Treatment: tissue, lung/untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

16

Rikova K (2010) CST Curation Set: 9458; Year: 2010; Biosample/Treatment: tissue, lung/untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

17

Alberobello AT, et al. (2010) Selective disruption of insulin-like growth factor-1 (IGF-1) signaling via phosphoinositide-dependent kinase-1 prevents the protective effect of IGF-1 on human cancer cell death. J Biol Chem 285, 6563-72
20044479   Curated Info

18

Dettori R, et al. (2009) Regulation of the interaction between protein kinase C-related protein kinase 2 (PRK2) and its upstream kinase, 3-phosphoinositide-dependent protein kinase 1 (PDK1). J Biol Chem 284, 30318-27
19723632   Curated Info

19

Daub H, et al. (2008) Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell 31, 438-48
18691976   Curated Info

20

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

21

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

22

Tan NY, et al. (2008) Angiotensin II-inducible platelet-derived growth factor-D transcription requires specific Ser/Thr residues in the second zinc finger region of Sp1. Circ Res 102, e38-51
18258854   Curated Info

23

Defer N, Azroyan A, Pecker F, Pavoine C (2007) TNFR1 and TNFR2 signaling interplay in cardiac myocytes. J Biol Chem 282, 35564-73
17913704   Curated Info

24

Wu SC, Solaro RJ (2007) Protein kinase C zeta. A novel regulator of both phosphorylation and de-phosphorylation of cardiac sarcomeric proteins. J Biol Chem 282, 30691-8
17724026   Curated Info

25

Ranganathan S, et al. (2007) Activation loop phosphorylation-independent kinase activity of human protein kinase C zeta. Proteins 67, 709-19
17335005   Curated Info

26

Zhang Y, Liao M, Dufau ML (2006) Phosphatidylinositol 3-kinase/protein kinase Czeta-induced phosphorylation of Sp1 and p107 repressor release have a critical role in histone deacetylase inhibitor-mediated derepression [corrected] of transcription of the luteinizing hormone receptor gene. Mol Cell Biol 26, 6748-61
16943418   Curated Info

27

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

28

Weigert C, et al. (2005) The phosphorylation of Ser318 of insulin receptor substrate 1 is not per se inhibitory in skeletal muscle cells but is necessary to trigger the attenuation of the insulin-stimulated signal. J Biol Chem 280, 37393-9
16129678   Curated Info

29

Magid R, Davies PF (2005) Endothelial protein kinase C isoform identity and differential activity of PKCzeta in an athero-susceptible region of porcine aorta. Circ Res 97, 443-9
16051884   Curated Info

30

Kim JH, et al. (2005) Novel functions of the phospholipase D2-Phox homology domain in protein kinase Czeta activation. Mol Cell Biol 25, 3194-208
15798205   Curated Info

31

Richter EA, et al. (2004) Differential effect of bicycling exercise intensity on activity and phosphorylation of atypical protein kinase C and extracellular signal-regulated protein kinase in skeletal muscle. J Physiol 560, 909-18
15297577   Curated Info

32

Castoria G, et al. (2004) Role of atypical protein kinase C in estradiol-triggered G1/S progression of MCF-7 cells. Mol Cell Biol 24, 7643-53
15314172   Curated Info

33

Teusch N, Lombardo E, Eddleston J, Knaus UG (2004) The low molecular weight GTPase RhoA and atypical protein kinase Czeta are required for TLR2-mediated gene transcription. J Immunol 173, 507-14
15210811   Curated Info

34

Smith L, Wang Z, Smith JB (2003) Caspase processing activates atypical protein kinase C zeta by relieving autoinhibition and destabilizes the protein. Biochem J 375, 663-71
12887331   Curated Info

35

Shenoy NG, Gleich GJ, Thomas LL (2003) Eosinophil major basic protein stimulates neutrophil superoxide production by a class IA phosphoinositide 3-kinase and protein kinase C-zeta-dependent pathway. J Immunol 171, 3734-41
14500673   Curated Info

36

Martelli AM, et al. (2003) A new selective AKT pharmacological inhibitor reduces resistance to chemotherapeutic drugs, TRAIL, all-trans-retinoic acid, and ionizing radiation of human leukemia cells. Leukemia 17, 1794-805
12970779   Curated Info

37

Guizzetti M, Möller T, Costa LG (2003) Ethanol inhibits muscarinic receptor-mediated DNA synthesis and signal transduction in human fetal astrocytes. Neurosci Lett 344, 68-70
12781924   Curated Info

38

Jiang G, et al. (2003) Salicylic acid reverses phorbol 12-myristate-13-acetate (PMA)- and tumor necrosis factor alpha (TNFalpha)-induced insulin receptor substrate 1 (IRS1) serine 307 phosphorylation and insulin resistance in human embryonic kidney 293 (HEK293) cells. J Biol Chem 278, 180-6
12409308   Curated Info

39

Dong LQ, et al. (1999) Primary structure, tissue distribution, and expression of mouse phosphoinositide-dependent protein kinase-1, a protein kinase that phosphorylates and activates protein kinase Czeta. J Biol Chem 274, 8117-22
10075713   Curated Info