Transforming growth factor (TGF)-β production, secretion, and activation. Some elements of protein processing and post-translation modifications involved in the regulatory control of TGF-β are depicted. The TGF-β1 gene encodes a 390 amino acid polypeptide that is cleaved into two polypeptides that form homodimers during protein processing: latency-associated peptide (LAP) and TGF-β. These homodimers are noncovalently associated to form the small latent TGF-β complex, which is secreted. Alternatively, this complex can be covalently linked by disulfide bonds to a latent TGF-β binding protein (LTBP) before secretion. LTBP provides means of anchoring latent TGF (LTGF)-β in the extracellular matrix (ECM), which may involve cross-linking by transglutaminase and which requires proteolytic processing to release LTGF-β before activation. Activation occurs extracellularly to release TGF-β at or near the cell surface so that it immediately binds to its receptors. TGF-β receptors I and II form a heterocomplex that signals via the SMAD signal transduction protein family.TGF-β receptor III, also known as betaglycan, is nonsignaling but may be involved in presenting TGF-β to its signaling receptors.