Fig. 3.

The TGF-β signaling pathway. At the BBB, TGF-β signaling is mediated by two distinct receptors designated ALK-1 and ALK-5. Activation of ALK-1 by binding of BMP-9 triggers phosphorylation of Smads 1, 5, and 8, while activation of ALK-5 via TGF-β, triggers phosphorylation of Smads 2 and 3. Once phosphorylated, these Smad signal-transducing proteins bind to the common Smad (i.e., Smad4) and form a complex that translocate into the nucleus and regulate transcription of target genes