Transforming growth factor beta 1 (TGF-β1) is a member of the transforming growth factor beta superfamily of cytokines. TGF-ß1 precursor contains 390 amino acids with an N-terminal signal peptide of 29 amino acids required for secretion from a cell, a 249 amino acids pro-region ( latency associated peptide or LAP), and a 112 amino acids C-terminal region that becomes the active TGF-β 1 upon activation.
Both LAP and TGF-ß1 exist as homodimers in circulation, but the disulfide linked homodimers of LAP and TGF-β1 remain non-covalently associated, forming the small latent TGFβ1 complex (SLC, 100 kD). The large latent TGF- β1 Complex (LLC, 235 – 260 kD) contains a third component, the latent TGF- β binding protein (LTBP), which is linked to LAP by a single disulfide bond. The LTBP does not confer latency, but for efficient secretion of the complex to extracellular sites. Free active TGF-β1 can be released (activated) by many factors including enzymes and low or high pH. The following picture illustrates the relationship among different forms of TGF-ß1.
TGF-β1 is nearly 100% conserved across mammalian species. It has diverse biological functions in multiple cellular processes such as regulating proliferation and differentiation of various cell types. TGF-ß1 is also an important immunoregulatory cytokine, which is involved in the maintenance of self-tolerance, Th17 differentiation, and T cell homeostasis etc.