e_re249( EMT ):
SARA interacts directly with Smad2 and Smad3
The C-ter of SARA interacts TGFBR1 and TGFBR2
SARA presents Smad2 to the TGFb receptor
Phosphorylation of Smad2 induces dissociation from SARA with concomitant formation of Smad2-Smad4 complexes and nuclear translocation.
Small GTPases such as Rab5 catalyse movement of activated receptor complexes to early endosomal compartments
Here, the complex encounter SARA: a phospholipid-bound carrier
SARA presents Smads to the TGFBR1
The ligand bound activated receptor complex is internalized via endocytosis
2 pathways of receptor complex endocytosis: clathrin-mediated or caveolae-mediated
Through the clathrin pathway, activated ligan-receptor complex are brought into early endosomes which are enriched with scaffold proteins such as SARA.
Clathrin-dependent internalization into endosome, where the Smad2 anchor SARA is enriched, promotes TGFB signalling.
Raft-caveolar internalization pathway contains the Smad7-Smurf2 bound receptor and is required for rapid receptor turnover.
Thus, segregation of TGF-b receptors into distinct endocytic compartments regulates Smad activation and receptor turnover
e_re217( EMT ):
Smad2 and Smad3 interacted with TGFBR1 after it was phosphorylated by TGFBR2
TGFB1 induced phosphorylation of Smad2 and Smad3
Participates in complexes:
In compartment: Early Endosome
Participates in reactions:
As Reactant or Product:
- SARA*@Early Endosome + TGFB1|hm2:TGFBR1|Ser_pho|hm2:TGFBR2|Ser_pho|hm2@Cytoplasm → SARA*:TGFB1|hm2:TGFBR1|Ser_pho|hm2:TGFBR2|Ser_pho|hm2@Early Endosome