TGF-β / Smad Signaling - Pulmonary Arterial Hypertension
Transforming growth factor beta (TGF-β)/Smad signaling pathway is involved in a number of cellular processes, including cell growth, differentiation, motility and adhesion etc. This signaling pathway plays a crucial part in mammalian development as well as in tumor suppression through inhibition of proliferation and induction of apoptosis in multiple cell types.
The TGF-β family is generally classified into two sub-families, TGF-β ligands, and bone morphogenic protein (BMP) ligands. In canonical signaling, receptor activation lead to phosphorylation of a group of transcription factors called Smads. TGF-β ligands bind to type II receptors (TGF-β II) which recruit and phosphorylate type I receptor (TGF-β I) on serine/threonine residues. The TGF-β I then recruits and phosphorylates a receptor regulated Smad (R-Smad). The R-Smad binds to the common Smad (Co-Smad) and forms a heterodimeric complex. This complex then translocates into the cell nucleus where it binds with nuclear co-factors to regulate the transcription of various target genes. Dysregulation of TGF-β/Smad signaling pathway is associated with a number of pathological conditions including fibrosis, cancer, immunodeficiency, diabetes and cardiovascular diseases etc.