Thr179
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Home > Phosphorylation Site Page: > Thr179  -  SMAD3 (human)

Site Information
PQSNIPEtPPPGYLS   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 451177

In vivo Characterization
Methods used to characterize site in vivo:
[32P] bio-synthetic labeling ( 11 , 12 ) , immunoprecipitation ( 6 , 7 ) , mutation of modification site ( 1 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ) , phospho-antibody ( 1 , 2 , 3 , 4 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ) , western blotting ( 1 , 2 , 3 , 4 , 6 , 7 , 8 , 10 , 12 )
Disease tissue studied:
breast cancer ( 1 , 2 , 5 , 10 ) , cervical cancer ( 7 ) , cervical adenocarcinoma ( 7 ) , liver cancer ( 2 ) , lung cancer ( 3 ) , non-small cell lung cancer ( 3 ) , non-small cell lung adenocarcinoma ( 3 ) , melanoma skin cancer ( 4 )
Relevant cell line - cell type - tissue:

Upstream Regulation
Regulatory protein:
HRas (human) ( 12 ) , MEK1 (human) ( 12 ) , NOX4 (human) ( 2 ) , SMAD4 (human) ( 7 ) , TGFB1 (human) ( 1 )
Putative in vivo kinases:
Akt1 (human) ( 3 ) , CDK2 (mouse) ( 11 ) , CDK4 (mouse) ( 5 , 11 ) , CDK8 (human) ( 7 ) , CDK9 (human) ( 7 ) , OSR1 (human) ( 1 )
Kinases, in vitro:
CDK8 (human) ( 7 ) , CDK9 (human) ( 7 ) , ERK2 (human) ( 9 , 12 ) , OSR1 (human) ( 1 )
Treatments:
alvocidib ( 8 ) , BMP2 ( 7 ) , DPI ( 2 ) , EGF ( 6 , 8 , 9 , 12 ) , H2O2 ( 2 ) , kaempferol ( 3 ) , LTB4 ( 2 ) , PD98059 ( 9 , 12 ) , SB203580 ( 10 ) , SB431542 ( 8 ) , siRNA ( 1 ) , TGF-beta ( 3 , 6 , 7 , 8 , 10 ) , U0126 ( 2 , 8 , 9 ) , wortmannin ( 12 ) , Y27632 ( 10 )

Downstream Regulation
Effects of modification on SMAD3:
activity, inhibited ( 9 ) , intracellular localization ( 12 ) , molecular association, regulation ( 6 , 8 )
Effects of modification on biological processes:
carcinogenesis, induced ( 1 ) , cell cycle regulation ( 5 , 11 ) , cell growth, altered ( 12 ) , cell motility, induced ( 3 ) , signaling pathway regulation ( 1 ) , transcription, altered ( 7 , 11 , 12 ) , transcription, induced ( 1 ) , transcription, inhibited ( 5 )
Induce interaction with:
NEDD4L (human) ( 8 ) , PIN1 (human) ( 6 )

References 

1

Li Y, et al. (2020) OSR1 phosphorylates the Smad2/3 linker region and induces TGF-β1 autocrine to promote EMT and metastasis in breast cancer. Oncogene
33051597   Curated Info

2

Jeon WK, et al. (2015) The proinflammatory LTB4/BLT1 signal axis confers resistance to TGF-β1-induced growth inhibition by targeting Smad3 linker region. Oncotarget 6, 41650-66
26497676   Curated Info

3

Jo E, et al. (2015) Kaempferol Suppresses Transforming Growth Factor-β1-Induced Epithelial-to-Mesenchymal Transition and Migration of A549 Lung Cancer Cells by Inhibiting Akt1-Mediated Phosphorylation of Smad3 at Threonine-179. Neoplasia 17, 525-37
26297431   Curated Info

4

Cohen-Solal KA, et al. (2011) Constitutive Smad linker phosphorylation in melanoma: a mechanism of resistance to transforming growth factor-β-mediated growth inhibition. Pigment Cell Melanoma Res 24, 512-24
21477078   Curated Info

5

Zelivianski S, Cooley A, Kall R, Jeruss JS (2010) Cyclin-dependent kinase 4-mediated phosphorylation inhibits smad3 activity in cyclin d-overexpressing breast cancer cells. Mol Cancer Res 8, 1375-87
20736297   Curated Info

6

Matsuura I, et al. (2010) Pin1 promotes transforming growth factor-beta-induced migration and invasion. J Biol Chem 285, 1754-64
19920136   Curated Info

7

Alarcón C, et al. (2009) Nuclear CDKs drive Smad transcriptional activation and turnover in BMP and TGF-beta pathways. Cell 139, 757-69
19914168   Curated Info

8

Gao S, et al. (2009) Ubiquitin ligase Nedd4L targets activated Smad2/3 to limit TGF-beta signaling. Mol Cell 36, 457-68
19917253   Curated Info

9

Matsuura I, Wang G, He D, Liu F (2005) Identification and characterization of ERK MAP kinase phosphorylation sites in Smad3. Biochemistry 44, 12546-53
16156666   Curated Info

10

Kamaraju AK, Roberts AB (2005) Role of Rho/ROCK and p38 MAP kinase pathways in transforming growth factor-beta-mediated Smad-dependent growth inhibition of human breast carcinoma cells in vivo. J Biol Chem 280, 1024-36
15520018   Curated Info

11

Matsuura I, et al. (2004) Cyclin-dependent kinases regulate the antiproliferative function of Smads. Nature 430, 226-31
15241418   Curated Info

12

Kretzschmar M, Doody J, Timokhina I, Massagué J (1999) A mechanism of repression of TGFbeta/ Smad signaling by oncogenic Ras. Genes Dev 13, 804-16
10197981   Curated Info

13

Liu X, et al. (1997) Transforming growth factor beta-induced phosphorylation of Smad3 is required for growth inhibition and transcriptional induction in epithelial cells. Proc Natl Acad Sci U S A 94, 10669-74
9380693   Curated Info