Reactome: A Curated Pathway Database
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Phosphorylation of SMAD2 and SMAD3 linker regions by CDK8 or CDK9

Stable Identifier
R-HSA-2176475
Type
Reaction
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

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
Participants
Participant Of
This entity is regulated by:
Title Physical Entity Activity
protein serine/threonine kinase activity of CDK8:CCNC/ CDK9:CCNT [nucleoplasm] CDK8:CCNC/ CDK9:CCNT [nucleoplasm] protein serine/threonine kinase activity (0004674)
Orthologous Events