Phosphorylation of SMAD2 and SMAD3 linker regions by CDK8 or CDK9

Stable Identifier
R-HSA-2176475
Type
Reaction [transition]
Species
Homo sapiens
Compartment
ReviewStatus
5/5
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
CDK8 in complex with cyclin C (CDK8:CCNC) and CDK9 in complex with cyclin T (CDK9:CCNT) are able to phosphorylate the linker region of SMAD2 and SMAD3. In SMAD3, CDK8/CDK9 preferentially targets threonine residue T179, although serine residues S208 and S213 can also be phosphorylated. In SMAD2, CDK8/9 preferentially targets threonine residue T220 (corresponds to T190 in the short isoform of SMAD2, SMAD2-2). Phosphorylation of serine residues that correspond to serines S208 and S213 of SMAD3 has not been examined. Phosphorylation of the linker region of SMAD2 and SMAD3 by CDK8/CDK9 enhances transcriptional activity of SMAD2/3:SMAD4 complex, but also primes SMAD2 and SMAD3 for ubiquitination and subsequent degradation (Alarcon et al. 2009).
Literature References
PubMed ID Title Journal Year
19914168 Nuclear CDKs drive Smad transcriptional activation and turnover in BMP and TGF-beta pathways

Xi, Q, Zaromytidou, AI, Pan, D, Miller, AN, Macias, MJ, Barlas, A, Manova-Todorova, K, Yu, J, Massague, J, Gao, S, Sapkota, G, Alarcon, C, Fujisawa, S

Cell 2009
Participants
Participates
Catalyst Activity

protein serine/threonine kinase activity of CDK8:CCNC/ CDK9:CCNT [nucleoplasm]

Orthologous Events
Authored
Reviewed
Created
Cite Us!