p-2S-SMAD2/3:SMAD4 p-T,2S-SMAD2/3:SMAD4 Phosphorylation of SMAD2 and SMAD3 linker regions by CDK8 or CDK9 Authored: Orlic-Milacic, M, 2012-04-04 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). EC Number: 2.7.11 Edited: Jassal, B, 2012-04-10 Pubmed19914168 Reactome Database ID Release 432176475 Reactome, http://www.reactome.org ReactomeREACT_121336 Reviewed: Huang, Tao, 2012-05-14 has a Stoichiometric coefficient of 2