TGF beta 1

Alias: Transforming Growth Factor beta-1

TGFβ is a pleiotropic immunoregulatory cytokine that controls immune responses. TGFβ1 is highly expressed in platelets and also produced by macrophages, lymphocytes, endothelial cells, chondrocytes, and leukemic cells. TGFβ is produced in a pro-form (pro-TGFβ) and is intracellularly cleaved by furin into latent TGFβ. Latent TGFβ is a non-covalently associated complex consisting of Latency-Associated Peptide (LAP) that is the N-terminal portion of pro-TGFβ and the mature TGFβ that is made of the C-terminus of pro-TGFβ. TGFβ is secreted as an inactive (latent) form in a complex with two proteins; LAP (Latency Activated Peptide) and LTBP (Latent TFGβ Binding Protein). Disassociation from this complex is required for its activation that occurs through various means that include low pH, reactive oxygen species, proteases, and several integrins. In this latent form, TGFβ cannot bind the TGFβ receptor and requires activation to become biologically active. In its active form, TGFβ binds to a heterodimeric receptor serine/threonine kinase complex that is comprised of TGFβR1 and TGFβRII. The binding of TGFβ to its receptor results in the phosphorylation/activation of the transcription factors SMAD2/3 that leads to their binding to SMAD4 and subsequent translocation to the nucleus. TGFβ activities include the inhibition of cell growth in epithelial cells, endothelial cells, fibroblasts, neurons, NK cells, T cells, and other hematopoietic cell types. TGFβ1 also downregulates the activities of activated macrophages and blocks the anti-tumor activity of IL-2 – bearing lymphokine-activated killer (LAK) cells. TGFβ1 has also been found to have a critical role in the development of TReg cells and act as a co-stimulatory factor for expression of Foxp3. These TGFβ1-induced regulatory T cells have been termed iTReg. Additionally, TGFβ1 and IL-6 together, can induce differentiation of mouse naive T cells into TH17 cells.