Reactome: A Curated Pathway Database

Phosphorylation of SMAD2 and SMAD3 linker regions by CDK8 or CDK9 (R-HSA-2176475) [Homo sapiens]


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).

Additional Information
Compartment nucleoplasm
Components of this entry
Input entries
Output entries
Catalyst Activity
PhysicalEntity Activity Active Units
CDK8:CCNC/ CDK9:CCNT protein serine/threonine kinase activity (0004674)  
Literature References
pubMedId Title Journal Year
19914168 Nuclear CDKs drive Smad transcriptional activation and turnover in BMP and TGF-beta pathways Cell 2009