Thr186
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Home > Phosphorylation Site Page: > Thr186  -  CDK9 (human)

Site Information
NSQPNRYtNRVVTLW   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 450950

In vivo Characterization
Methods used to characterize site in vivo:
[32P] bio-synthetic labeling ( 24 , 40 ) , immunoprecipitation ( 2 , 21 , 24 , 37 , 39 ) , mass spectrometry ( 2 , 3 , 4 , 10 , 11 , 13 , 15 , 16 , 17 , 18 , 19 , 20 , 22 , 23 , 25 , 26 , 28 , 29 , 30 , 31 , 32 , 33 , 35 , 38 ) , mutation of modification site ( 2 , 24 , 27 , 37 , 39 , 40 , 41 ) , phospho-antibody ( 5 , 6 , 14 , 24 , 27 , 34 , 37 ) , western blotting ( 1 , 2 , 5 , 6 , 14 , 24 , 34 , 37 , 39 , 41 )
Disease tissue studied:
HER2 positive breast cancer ( 3 ) , luminal A breast cancer ( 3 ) , luminal B breast cancer ( 3 ) , breast cancer, surrounding tissue ( 3 ) , breast cancer, triple negative ( 3 ) , cervical cancer ( 30 ) , cervical adenocarcinoma ( 30 ) , colorectal cancer ( 38 ) , colorectal carcinoma ( 38 ) , leukemia ( 1 , 2 ) , acute myelogenous leukemia ( 1 ) , acute monoblastic leukemia (M5a) or acute monocytic leukemia (M5b) ( 1 ) , T cell leukemia ( 2 ) , lung cancer ( 10 ) , non-small cell lung cancer ( 10 ) , lymphoma ( 1 )
Relevant cell line - cell type - tissue:

Upstream Regulation
Regulatory protein:
CAMK1D (human) ( 14 ) , NIPP-1 (human) ( 21 ) , PPP1CA (human) ( 37 ) , PPP2CB (human) ( 37 )
Kinases, in vitro:
CDK9 (human) ( 36 )
Putative upstream phosphatases:
PPP1CA (human) ( 24 , 37 ) , PPPM1A (human) ( 34 )
Phosphatases, in vitro:
PPM1B (human) ( 34 ) , PPP1CA (human) ( 37 ) , PPPM1A (human) ( 34 )
Treatments:
actinomycin_D ( 41 ) , alvocidib ( 5 ) , AZD2014 ( 1 ) , calyculin_A ( 37 ) , ciclosporin ( 37 ) , DRB ( 41 ) , FK506 ( 37 ) , HMBA ( 37 ) , ionomycin ( 14 ) , KN-92 ( 14 ) , KN-93 ( 14 ) , LLnL ( 14 ) , microcystin-LR ( 37 ) , nifedipine ( 37 ) , okadaic_acid ( 6 , 24 ) , phorbol_ester ( 14 ) , rapamycin ( 1 ) , siRNA ( 37 ) , small_molecule_activator_of_PP1 ( 6 ) , thapsigargin ( 14 ) , UV ( 37 ) , W-7 ( 14 , 37 )

Downstream Regulation
Effects of modification on CDK9:
enzymatic activity, induced ( 24 , 39 ) , molecular association, regulation ( 2 , 21 , 37 , 39 , 41 ) , protein stabilization ( 14 )
Effects of modification on biological processes:
transcription, altered ( 39 , 41 ) , transcription, inhibited ( 37 )
Induce interaction with:
EDG-1 (human) ( 41 ) , HEXIM1 (human) ( 37 ) , RNA ( 21 , 41 ) , TEAD1 (human) ( 39 )
Inhibit interaction with:
BRD4 (human) ( 37 ) , HSP90A (human) ( 2 )

References 

1

Beauchamp EM, et al. (2018) Identification and targeting of novel CDK9 complexes in acute myeloid leukemia. Blood
30587525   Curated Info

2

Mbonye U, et al. (2018) Cyclin-dependent kinase 7 (CDK7)-mediated phosphorylation of the CDK9 activation loop promotes P-TEFb assembly with Tat and proviral HIV reactivation. J Biol Chem
29743242   Curated Info

3

Mertins P, et al. (2016) Proteogenomics connects somatic mutations to signalling in breast cancer. Nature 534, 55-62
27251275   Curated Info

4

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
26506913   Curated Info

5

Yeh YY, et al. (2015) Up-regulation of CDK9 kinase activity and Mcl-1 stability contributes to the acquired resistance to cyclin-dependent kinase inhibitors in leukemia. Oncotarget 6, 2667-79
25596730   Curated Info

6

Tyagi M, et al. (2015) Reactivation of latent HIV-1 provirus via targeting protein phosphatase-1. Retrovirology 12, 63
26178009   Curated Info

7

Mertins P, et al. (2014) Ischemia in tumors induces early and sustained phosphorylation changes in stress kinase pathways but does not affect global protein levels. Mol Cell Proteomics 13, 1690-704
24719451   Curated Info

8

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
23312004   Curated Info

9

Mbonye UR, et al. (2013) Phosphorylation of CDK9 at Ser175 enhances HIV transcription and is a marker of activated P-TEFb in CD4(+) T lymphocytes. PLoS Pathog 9, e1003338
23658523   Curated Info

10

Klammer M, et al. (2012) Phosphosignature predicts dasatinib response in non-small cell lung cancer. Mol Cell Proteomics 11, 651-68
22617229   Curated Info

11

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
22496350   Curated Info

12

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
22424773   Curated Info

13

Mulhern D (2012) CST Curation Set: 13830; Year: 2012; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: (K/R)XpSX(K/R)
Curated Info

14

Ramakrishnan R, Rice AP (2012) Cdk9 T-loop phosphorylation is regulated by the calcium signaling pathway. J Cell Physiol 227, 609-17
21448926   Curated Info

15

Guo A (2011) CST Curation Set: 12078; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pTDXEAntibodies Used to Purify Peptides prior to LCMS: Phospho(Ser/Thr) CK2 Substrate (P-S/T3-100) Rabbit mAb Cat#: 8738
Curated Info

16

Guo A (2011) CST Curation Set: 12059; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pTXR
Curated Info

17

Guo A (2011) CST Curation Set: 12060; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pTXR
Curated Info

18

Guo A (2011) CST Curation Set: 12061; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pTXR
Curated Info

19

Guo A (2011) CST Curation Set: 12062; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pTXR
Curated Info

20

Guo A (2011) CST Curation Set: 12064; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pTXR Antibodies Used to Purify Peptides prior to LCMS: Phospho-Threonine-X-Arginine Antibody Cat#: 2351, PTMScan(R) Phospho-Thr-X-Arg Motif (T*XR) Immunoaffinity Beads Cat#: 1988
Curated Info

21

Ammosova T, et al. (2011) Expression of a protein phosphatase 1 inhibitor, cdNIPP1, increases CDK9 threonine 186 phosphorylation and inhibits HIV-1 transcription. J Biol Chem 286, 3798-804
21098020   Curated Info

22

Guo A (2011) CST Curation Set: 11116; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]Q Antibodies Used to Purify Peptides prior to LCMS: Phospho(Ser/Thr) ATM/ATR Substrate Antibody (polyAB) Cat#: 3005, PTMScan(R) Phospho-ATM/ATR Substrate Motif (pS/pTQ) Immunoaffinity Beads Cat#: 1980
Curated Info

23

Rigbolt KT, et al. (2011) System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal 4, rs3
21406692   Curated Info

24

Ammosova T, et al. (2011) Protein Phosphatase-1 Activates CDK9 by Dephosphorylating Ser175. PLoS One 6, e18985
21533037   Curated Info

25

Possemato A (2010) CST Curation Set: 10872; Year: 2010; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: (F/Y/M)Xp[ST](L/I/M)
Curated Info

26

Christensen GL, et al. (2010) Quantitative phosphoproteomics dissection of seven-transmembrane receptor signaling using full and biased agonists. Mol Cell Proteomics 9, 1540-53
20363803   Curated Info

27

Dow EC, Liu H, Rice AP (2010) T-loop phosphorylated Cdk9 localizes to nuclear speckle domains which may serve as sites of active P-TEFb function and exchange between the Brd4 and 7SK/HEXIM1 regulatory complexes. J Cell Physiol 224, 84-93
20201073   Curated Info

28

Dulla K, et al. (2010) Quantitative site-specific phosphorylation dynamics of human protein kinases during mitotic progression. Mol Cell Proteomics 9, 1167-81
20097925   Curated Info

29

Schreiber TB, et al. (2010) An integrated phosphoproteomics work flow reveals extensive network regulation in early lysophosphatidic acid signaling. Mol Cell Proteomics 9, 1047-62
20071362   Curated Info

30

Olsen JV, et al. (2010) Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal 3, ra3
20068231   Curated Info

31

Pan C, Olsen JV, Daub H, Mann M (2009) Global effects of kinase inhibitors on signaling networks revealed by quantitative phosphoproteomics. Mol Cell Proteomics 8, 2796-808
19651622   Curated Info

32

Possemato A (2009) CST Curation Set: 7978; Year: 2009; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]Q Antibodies Used to Purify Peptides prior to LCMS: Phospho(Ser/Thr) ATM/ATR Substrate Antibody (polyAB) Cat#: 3005, PTMScan(R) Phospho-ATM/ATR Substrate Motif (pS/pTQ) Immunoaffinity Beads Cat#: 1980
Curated Info

33

Oppermann FS, et al. (2009) Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics 8, 1751-64
19369195   Curated Info

34

Wang Y, et al. (2008) Phosphatase PPM1A regulates phosphorylation of Thr-186 in the Cdk9 T-loop. J Biol Chem 283, 33578-84
18829461   Curated Info

35

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

36

Baumli S, et al. (2008) The structure of P-TEFb (CDK9/cyclin T1), its complex with flavopiridol and regulation by phosphorylation. EMBO J 27, 1907-18
18566585   Curated Info

37

Chen R, et al. (2008) PP2B and PP1alpha cooperatively disrupt 7SK snRNP to release P-TEFb for transcription in response to Ca2+ signaling. Genes Dev 22, 1356-68
18483222   Curated Info

38

Wissing J, et al. (2007) Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry. Mol Cell Proteomics 6, 537-47
17192257   Curated Info

39

Li Q, et al. (2005) Analysis of the large inactive P-TEFb complex indicates that it contains one 7SK molecule, a dimer of HEXIM1 or HEXIM2, and two P-TEFb molecules containing Cdk9 phosphorylated at threonine 186. J Biol Chem 280, 28819-26
15965233   Curated Info

40

Ammosova T, et al. (2005) Dephosphorylation of CDK9 by protein phosphatase 2A and protein phosphatase-1 in Tat-activated HIV-1 transcription. Retrovirology 2, 47
16048649   Curated Info

41

Chen R, Yang Z, Zhou Q (2004) Phosphorylated positive transcription elongation factor b (P-TEFb) is tagged for inhibition through association with 7SK snRNA. J Biol Chem 279, 4153-60
14627702   Curated Info