Ser208
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Home > Phosphorylation Site Page: > Ser208  -  SMAD3 (human)

Site Information
DAGsPNLsPNPMsPA   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 451179

In vivo Characterization
Methods used to characterize site in vivo:
[32P] bio-synthetic labeling ( 13 ) , immunoprecipitation ( 6 , 7 ) , mutation of modification site ( 1 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 13 ) , phospho-antibody ( 1 , 2 , 3 , 4 , 6 , 7 , 8 , 9 , 10 , 11 , 13 ) , western blotting ( 1 , 2 , 3 , 4 , 6 , 7 , 8 , 9 , 11 , 13 )
Disease tissue studied:
breast cancer ( 2 , 5 , 11 ) , 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) ( 13 ) , MEK1 (human) ( 9 , 13 ) , NOX4 (human) ( 2 )
Putative in vivo kinases:
CDK4 (human) ( 5 ) , ERK1 (rat) ( 1 ) , ERK2 (rat) ( 1 )
Kinases, in vitro:
CDK8 (human) ( 7 ) , CDK9 (human) ( 7 ) , ERK2 (human) ( 7 , 10 , 12 , 13 )
Treatments:
alvocidib ( 7 , 8 ) , bacterial biofilm ( 1 ) , DPI ( 2 ) , EGF ( 6 , 8 , 10 , 13 ) , FSL-1 ( 1 ) , gelatin ( 9 ) , H2O2 ( 2 ) , HB-EGF ( 1 ) , LTB4 ( 2 ) , PD184352 ( 1 ) , PD98059 ( 10 , 13 ) , SB203580 ( 11 ) , SB431542 ( 8 ) , TGF-alpha ( 1 ) , TGF-beta ( 6 , 7 , 8 , 9 , 11 ) , U0126 ( 2 , 8 , 10 ) , wortmannin ( 13 ) , Y27632 ( 11 )

Downstream Regulation
Effects of modification on SMAD3:
activity, inhibited ( 1 , 10 ) , intracellular localization ( 13 )
Effects of modification on biological processes:
cell growth, altered ( 13 ) , signaling pathway regulation ( 1 ) , transcription, altered ( 11 , 13 ) , transcription, inhibited ( 1 , 5 )

References 

1

Bi J, et al. (2019) Epidermal growth factor receptor signaling suppresses αvβ6 integrin and promotes periodontal inflammation and bone loss. J Cell Sci 133
31722981   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

Hayashida T, et al. (2007) MAP-kinase activity necessary for TGFbeta1-stimulated mesangial cell type I collagen expression requires adhesion-dependent phosphorylation of FAK tyrosine 397. J Cell Sci 120, 4230-40
18032789   Curated Info

10

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

11

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

12

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

13

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

14

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