Recombinant Human TGF-beta 3 Protein, CF New

TGF­ beta 3 (transforming growth factor-beta 3) is a member of a TGF-beta superfamily subgroup that is defined by their structural and functional similarities (1-5). TGF-beta 3 and its closely related proteins, TGF-beta 1 and ­-beta 2, act as cellular switches to regulate immune function, cell proliferation, and epithelial­-mesenchymal transition (4, 6, 7). The non-redundant biological effects of TGF-beta 3 include involvement in palatogenesis, chondrogenesis, and pulmonary development (1, 2, 7-9). Human TGF-­ beta 3 cDNA encodes a 412 amino acid (aa) precursor that contains a 20 aa signal peptide and a 392 aa proprotein. The proprotein is processed by a furin­like convertase to generate a 220 aa latency­associated peptide (LAP) and a 112 aa mature TGF­-beta 3 (10, 11). Mature human TGF­-beta 3 shows 100%, 99%, and 98% aa identity with mouse/dog/horse, rat, and pig TGF-­ beta 3, respectively. TGF-beta 3 is secreted as a complex with LAP. This latent form of TGF-beta 3 becomes active upon cleavage by plasmin, matrix metalloproteases, thrombospondin-1, and a subset of integrins (12). TGF-beta 3 binds with high affinity to TGF-beta RII, a type II serine/threonine kinase receptor. This receptor then phosphorylates and activates type I serine/threonine kinase receptors, TGF-­ beta RI or ALK-­1, to modulate transcription through Smad phosphorylation (13-15). The divergent biological effects exerted by individual TGF-beta isoforms is dependent upon the recruitment of co-receptors (TGF-­ beta RIII and endoglin) and the subsequent initiation of Smad-­dependent or -independent signaling pathways (14, 16, 17).