TGF-beta Antibody

Transforming growth factor-β (TGF-β) proteins belong to the TGF-β superfamily of cytokines that play a critical role in regulating cell proliferation and differentiation, developmental patterning and morphogenesis, and disease pathogenesis (1-3). TGF-β ligands elicit signaling through three cell surface receptors: type I (RI), type II (RII), and type III (RIII) TGF-β receptors. Type I and type II receptors are serine/threonine kinases that form a heteromeric complex following ligand binding to the type II receptor. In response to ligand binding, the type II receptors form a stable complex with the type I receptors, triggering phosphorylation and activation of the type I receptor (4). This results in the recruitment of receptor-mediated SMADs (SMAD2, SMAD3), which are phosphorylated by the type I kinase in an SSXS domain in the C-terminus. This leads to recruitment of the co-SMAD (SMAD4), and subsequent translocation of this heteromeric SMAD complex to the nucleus, where it regulates transcription of target genes (5-7). The type III receptor, also known as betaglycan, is a transmembrane proteoglycan with a large extracellular domain that binds TGF-β with high affinity but lacks a cytoplasmic signaling domain. Expression of the type III receptor can regulate TGF-β signaling through presentation of the ligand to the signaling complex (8).There are three TGF-beta family members, designated TGF-β1, TGF-β2, and TGF-β3, which are encoded by distinct genes and are expressed in a tissue specific manner (10). TGF-β proteins are synthesized as precursor proteins that are cleaved and reassembled in association with other proteins to form latent complexes. Activation occurs by proteolytic release of TGF-β monomers, which dimerize to form the mature TGF-β ligands. 1.Massagué, J. et al. (2000) Cell 103, 295-309. 2.de Caestecker, M.P. et al. (2000) J Natl Cancer Inst 92, 1388-402. 3.Derynck, R. et al. (2001) Nat Genet 29, 117-29. 4.Derynck, R. and Feng, X.H. (1997) Biochim Biophys Acta 1333, F105-50. 5.Miyazono, K. et al. (2000) Adv Immunol 75, 115-57. 6.Massagué, J. (2000) Nat Rev Mol Cell Biol 1, 169-78. 7.Derynck, R. et al. (1998) Cell 95, 737-40. 8.López-Casillas, F. et al. (1991) Cell 67, 785-95. 9.Kingsley, D.M. (1994) Genes Dev 8, 133-46.