TGFBR1/ALK-5 Protein, Human (Active, sf9, His-GST)

The transmembrane serine/threonine kinase, TGFBR1 (ALK-5), collaborates with the TGF-beta type II serine/threonine kinase receptor, TGFBR2, to form the dedicated receptor for TGF-beta cytokines, including TGFB1, TGFB2, and TGFB3. Serving as a signal transducer, TGFBR1 mediates the transmission of TGFB1, TGFB2, and TGFB3 signals from the cell surface to the cytoplasm, thereby orchestrating a diverse array of physiological and pathological processes. These include cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression, and carcinogenesis. The receptor complex, composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer, leads to the phosphorylation and activation of TGFBR1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2, causing its dissociation from the receptor and interaction with SMAD4. The resulting SMAD2-SMAD4 complex translocates to the nucleus, where it modulates the transcription of TGF-beta-regulated genes, constituting the canonical SMAD-dependent TGF-beta signaling cascade. Additionally, TGFBR1 is involved in non-canonical, SMAD-independent TGF-beta signaling pathways. For instance, it induces TRAF6 autoubiquitination, leading to MAP3K7 ubiquitination and activation, triggering apoptosis. TGFBR1 also regulates epithelial to mesenchymal transition through a SMAD-independent signaling pathway involving PARD6A phosphorylation and activation.