Table 1.
TGF-β receptor-interacting proteins that potentiate TGF-β signaling
| Interacting Protein | Regulatory Mechanism | References |
|---|---|---|
| SARA | Stabilizing R-Smads and TGF-β receptor association; Directing the activated receptor towards clathrin-mediated endocytic routing |
(58, 165, 166) |
| Hgs | Cooperating with SARA to stabilize TGF-β receptor:R-Smad association | (167) |
| cPML | Interacting with R-Smads and SARA to improve their association; Improving TGF-β receptor and SARA accumulation in early endosomes |
(168) |
| Axin | Adapter of Smad3 to facilitate its activation by TβRI; Forming a multimeric complex consisting of Smad7 and Arkadia to degrade Smad7 |
(74, 145, 153) |
| Dab2 | Associating with both TGF-β receptors and R-Smads to facilitate R-Smad activation; Promoting clathrin-mediated recycling of TβRII to protect it from degradation |
(169, 170) |
| TβRIII/betaglycan | Mediating Smad-independent activation of TRAF6-TAK1-p38 MAPK with TβRI | (171) |
| VE-cadherin | Enhancing TβRII:TβRI assembly into an active receptor complex to improve R-Smad phosphorylation. | (172) |
| Occludin | Regulating TβRI localization to enhance Smad activation | (173) |
| TRAF6 | Mediating the activation of p38 and JNK MAPK by ubiqitylation and phosphorylation of TAK1; Inhibiting TGF-β-induced R-Smad activation and IL-2 blockage in T cells |
(174–176) |
| Integrin αvβ3 | Interacting with TβRII to potentiate TGF-β1 activation | (177) |
| HSP90 | Binding to TβRI and TβRII to prevent Smurf2-mediated receptor ubiquitylation and degradation | (51) |
| Itch/AIP4 | Facilitating TGF-β receptor-Smad2 complex formation and enhancing TGF-β−induced transcription | (91) |
| CD44 | Associating with TβRI to promote Smad2/3 activation and PTH-rP expression | (178) |
| Mgat5 | Modifying N-glycans on TGF-β receptors to delay their removal at the cell surface by constitutive endocytosis | (179) |
| TLP | Associating with TβRI and TβRII to regulate the balance of Smad2 and Smad3 signaling by localizing Smad4 intracellularly | (180) |
| BAT3 | Interacting with TβRI and TβRII to potentiate Smad activation | (181) |
| km23-1 | Associating with TGF-β receptors and Smad2 in early endosomes to potentiate Smad activation | (182) |
| xIAP | Interacting with TβRI, mediating the activation of NF-κB by ubiquitiylation of TAK1, and coupling of Smad2/3 activation | (183) |