Curated Information
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Home > Curated Information Page > PubMed Id: 19914168
Alarcón C, et al. (2009) Nuclear CDKs drive Smad transcriptional activation and turnover in BMP and TGF-beta pathways. Cell 139, 757-69 19914168
This page summarizes selected information from the record referenced above and curated into PhosphoSitePlus®, a comprehensive online resource for the study of protein post-translational modifications (NAR, 2015, 43:D512-20). To learn more about the scope of PhosphoSitePlus®, click here.
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S187-p - SMAD1 (human)
Modsite: NSHPFPHsPNSSYPN SwissProt Entrez-Gene
Orthologous residues
SMAD1 (human): S187‑p, SMAD1 (mouse): S187‑p, SMAD1 (rat): S187‑p
Characterization
Methods used to characterize site in vivo immunoprecipitation, mutation of modification site, phospho-antibody, western blotting
Disease tissue studied:  cervical cancer, cervical adenocarcinoma
Relevant cell lines - cell types - tissues:  HaCaT (keratinocyte), HeLa S3 (cervical), MEF (fibroblast)
Cellular systems studied:  cell lines
Species studied:  human, mouse
Enzymes shown to modify site in vitro
Type Enzyme
KINASE CDK8 (human)
KINASE CDK9 (human)
KINASE ERK2 (human)

S195-p - SMAD1 (human)
Modsite: PNSSYPNsPGSSSSt SwissProt Entrez-Gene
Orthologous residues
SMAD1 (human): S195‑p, SMAD1 (mouse): S195‑p, SMAD1 (rat): S195‑p
Characterization
Methods used to characterize site in vivo immunoprecipitation, mutation of modification site, phospho-antibody, western blotting
Disease tissue studied:  cervical cancer, cervical adenocarcinoma
Relevant cell lines - cell types - tissues:  HaCaT (keratinocyte), HeLa S3 (cervical), MEF (fibroblast)
Cellular systems studied:  cell lines
Species studied:  human, mouse
Enzymes shown to modify site in vitro
Type Enzyme
KINASE CDK8 (human)
KINASE CDK9 (human)
KINASE ERK2 (human)

S206-p - SMAD1 (human)
Modsite: SSStYPHsPTSSDPG SwissProt Entrez-Gene
Orthologous residues
SMAD1 (human): S206‑p, SMAD1 (mouse): S206‑p, SMAD1 (rat): S206‑p
Characterization
Methods used to characterize site in vivo immunoprecipitation, mutation of modification site, phospho-antibody, western blotting
Disease tissue studied:  cervical cancer, cervical adenocarcinoma
Relevant cell lines - cell types - tissues:  HaCaT (keratinocyte), HeLa S3 (cervical), MEF (fibroblast)
Cellular systems studied:  cell lines
Species studied:  human, mouse
Enzymes shown to modify site in vitro
Type Enzyme
KINASE ERK2 (human)
KINASE CDK9 (human)
KINASE CDK8 (human)
Upstream Regulation
Potential in vivo enzymes for site: 
Type Enzyme Evidence Notes
KINASE CDK7 (human) activation of upstream enzyme, siRNA inhibition of enzyme
KINASE CDK9 (human) activation of upstream enzyme, siRNA inhibition of enzyme
KINASE CDK8 (human) co-immunoprecipitation, activation of upstream enzyme, siRNA inhibition of enzyme
Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
BMP2 increase in nuclear fraction
BMP2 SMAD1 (mouse) increase increase inhibited in mutants of C-terminal or linker phosphorylation sites
BMP2 SMAD4 (human) increase Smad4 -/- inhibits increase
BMP2 FOXO4 (human) increase FoxO4 siRNA inhibits
BMP2 SMURF1 (mouse) increase Smurf1 siRNA inhibits
MG132 BMP2 no effect upon treatment-induced increase
amanitin BMP2 no effect upon treatment-induced increase
U0126 BMP2 no effect upon treatment-induced increase
SB203580 BMP2 no effect upon treatment-induced increase
SP600125 BMP2 no effect upon treatment-induced increase
U0126, SB203580, SP600125 BMP2 no effect upon treatment-induced increase
alvocidib BMP2 inhibit treatment-induced increase
UV increase
UV SMAD1 (mouse) increase increase inhibited in mutants of linker phosphorylation sites
TGF-beta no change compared to control cytoplasmic and nuclear fractions
TGF-beta increase in nuclear fraction, not in cytosolic fraction
alvocidib TGF-beta inhibit treatment-induced increase
Downstream Regulation
Effect of modification (function):  molecular association, regulation
Effect of modification (process):  transcription, altered
Modification regulates interactions with: 
Interacting molecule Interacting domains Effect Consequences (function) Consequences (process) Detection assays
YAP1 (human) WW Induces transcription, altered co-immunoprecipitation

S214-p - SMAD1 (human)
Modsite: PTSSDPGsPFQMPAD SwissProt Entrez-Gene
Orthologous residues
SMAD1 (human): S214‑p, SMAD1 (mouse): S214‑p, SMAD1 (rat): S214‑p
Characterization
Methods used to characterize site in vivo immunoprecipitation, mutation of modification site, phospho-antibody, western blotting
Disease tissue studied:  cervical cancer, cervical adenocarcinoma
Relevant cell lines - cell types - tissues:  HaCaT (keratinocyte), HeLa S3 (cervical), MEF (fibroblast)
Cellular systems studied:  cell lines
Species studied:  human, mouse
Enzymes shown to modify site in vitro
Type Enzyme
KINASE CDK9 (human)
KINASE ERK2 (human)
KINASE CDK8 (human)
Downstream Regulation
Effect of modification (function):  molecular association, regulation
Modification regulates interactions with: 
Interacting molecule Interacting domains Effect Consequences (function) Consequences (process) Detection assays
YAP1 (human) WW Induces transcription, altered co-immunoprecipitation

T220-p - SMAD2 (human)
Modsite: QSNYIPEtPPPGYIS SwissProt Entrez-Gene
Orthologous residues
SMAD2 (human): T220‑p, SMAD2 (mouse): T220‑p, SMAD2 (rat): T220‑p, SMAD2 (cow): T220‑p
Characterization
Methods used to characterize site in vivo immunoprecipitation, phospho-antibody, western blotting
Relevant cell lines - cell types - tissues:  HaCaT (keratinocyte), MEF (fibroblast)
Cellular systems studied:  cell lines
Species studied:  human, mouse
Upstream Regulation
Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
BMP2 no change compared to control cytoplasmic and nuclear fractions
TGF-beta increase in nuclear fraction; not in cytosolic fraction
TGF-beta FOXO4 (human) increase FoxO4 siRNA decreases
TGF-beta NEDD4L (human) increase Nedd4L siRNA decreases (slightly)
MG132 decrease slight decrease

T179-p - SMAD3 (human)
Modsite: PQSNIPEtPPPGYLS SwissProt Entrez-Gene
Orthologous residues
SMAD3 (human): T179‑p, SMAD3 (mouse): T179‑p, SMAD3 (rat): T179‑p
Characterization
Methods used to characterize site in vivo immunoprecipitation, mutation of modification site, phospho-antibody, western blotting
Disease tissue studied:  cervical cancer, cervical adenocarcinoma
Relevant cell lines - cell types - tissues:  HaCaT (keratinocyte), HeLa S3 (cervical), MEF (fibroblast)
Cellular systems studied:  cell lines
Species studied:  human, mouse
Enzymes shown to modify site in vitro
Type Enzyme
KINASE CDK8 (human)
KINASE CDK9 (human)
Upstream Regulation
Potential in vivo enzymes for site: 
Type Enzyme Evidence Notes
KINASE CDK8 (human) activation of upstream enzyme, siRNA inhibition of enzyme
KINASE CDK9 (human) activation of upstream enzyme, siRNA inhibition of enzyme
Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
BMP2 no change compared to control cytoplasmic and nuclear fractions
TGF-beta increase in nuclear fraction; not in cytosolic fraction
TGF-beta SMAD4 (human) increase

S204-p - SMAD3 (human)
Modsite: NHSMDAGsPNLsPNP SwissProt Entrez-Gene
Orthologous residues
SMAD3 (human): S204‑p, SMAD3 (mouse): S204‑p, SMAD3 (rat): S204‑p
Characterization
Methods used to characterize site in vivo immunoprecipitation, mutation of modification site, phospho-antibody, western blotting
Disease tissue studied:  cervical cancer, cervical adenocarcinoma
Relevant cell lines - cell types - tissues:  HaCaT (keratinocyte), HeLa S3 (cervical), MEF (fibroblast)
Cellular systems studied:  cell lines
Species studied:  human, mouse
Enzymes shown to modify site in vitro
Type Enzyme
KINASE ERK2 (human)

S208-p - SMAD3 (human)
Modsite: DAGsPNLsPNPMsPA SwissProt Entrez-Gene
Orthologous residues
SMAD3 (human): S208‑p, SMAD3 (mouse): S208‑p, SMAD3 (rat): S208‑p
Characterization
Methods used to characterize site in vivo immunoprecipitation, mutation of modification site, phospho-antibody, western blotting
Disease tissue studied:  cervical cancer, cervical adenocarcinoma
Relevant cell lines - cell types - tissues:  HaCaT (keratinocyte), HeLa S3 (cervical), MEF (fibroblast)
Cellular systems studied:  cell lines
Species studied:  human, mouse
Enzymes shown to modify site in vitro
Type Enzyme
KINASE ERK2 (human)
KINASE CDK9 (human)
KINASE CDK8 (human)
Upstream Regulation
Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
TGF-beta increase in nuclear fraction, not in cytosolic fraction
alvocidib TGF-beta inhibit treatment-induced increase

S213-p - SMAD3 (human)
Modsite: NLsPNPMsPAHNNLD SwissProt Entrez-Gene
Orthologous residues
SMAD3 (human): S213‑p, SMAD3 (mouse): S213‑p, SMAD3 (rat): S213‑p
Characterization
Methods used to characterize site in vivo immunoprecipitation, mutation of modification site, phospho-antibody, western blotting
Disease tissue studied:  cervical cancer, cervical adenocarcinoma
Relevant cell lines - cell types - tissues:  HaCaT (keratinocyte), HeLa S3 (cervical), MEF (fibroblast)
Cellular systems studied:  cell lines
Species studied:  human, mouse
Enzymes shown to modify site in vitro
Type Enzyme
KINASE CDK8 (human)
KINASE ERK2 (human)
KINASE CDK9 (human)