TGF-beta Superfamily

Overview of TGF-beta Superfamily

TGF-beta superfamily is comprised of a large group of proteins, including the activin/inhibin family, bone morphogenetic proteins (BMPs), growth differentiation factors (GDFs), the TGF-beta subfamily, and glial cell line-derived neurotrophic factor (GDNF) family. TGF-beta superfamily has three types: TGF-beta 1, TGF-beta 2, and TGF-beta 3. TGF-beta superfamily proteins have been discovered in a variety of species, including invertebrates as well as vertebrates. TGF-beta superfamily members play fundamental roles in the regulation of various biological processes such as growth, development, tissue homeostasis and regulation of the immune system.

TGF-beta 1 / Transforming growth factor beta 1

TGF-beta 1 (Transforming growth factor beta 1), is a polypeptide member of the TGF-beta superfamily of cytokines. It is a secreted protein that performs many cellular functions, including the control of cell growth, cell proliferation, cell differentiation and apoptosis. In humans, TGF-beta is encoded by the TGFB1 gene. TGF-beta 1 was first identified in human platelets as a protein with a molecular mass of 25 kilodaltons with a potential role in wound healing. It was later characterized as a large protein precursor (containing 390 amino acids) that was proteolytically processed to produce a mature peptide of 112 amino acids. TGF-beta 1 plays an important role in controlling the immune system.

TGF-beta 2 / Transforming growth factor beta 2

TGF-beta 2 (Transforming growth factor-beta 2) is a secreted protein known as a cytokine that performs many cellular functions and has a vital role during embryonic development (alternative names: Glioblastoma-derived T-cell suppressor factor, G-TSF, BSC-1 cell growth inhibitor, Polyergin, Cetermin). It is an extracellular glycosylated protein. It is known to suppress the effects of interleukin dependent T-cell tumors. There are two named isoforms of this protein, created by alternative splicing of the same gene. Defects in TGF-beta 2 are the cause of Loeys-Dietz syndrome 4 (LDS4), which is characterized by arterial tortuosity, aortic dissection, intracranial aneurysm, etc.

TGF-beta 3 / Transforming growth factor beta 3

TGF-beta 3 (transforming growth factor beta 3) is a type of cytokines, which is involved in cell differentiation, embryogenesis and development. TGF-beta 3 can regulate molecules involved in cellular adhesion and extracellular matrix (ECM) formation during the process of palate development. TGF-β3 also plays an essential role in controlling the development of lungs in mammals, by also regulating cell adhesion and ECM formation in this tissue, and controls wound healing by regulating the movements of epidermal and dermal cells in injured skin. In a direct comparison between TGF-beta 3 and TGF-beta 1, TGF-beta 3 appeared to be three- to fivefold more potent than TGF-beta 1.

References

Hinck, A.P, et al. (1996) Transforming growth factor beta 1: three-dimensional structure in solution and comparison with the X-ray structure of transforming growth factor beta 2. Biochemistry. 35: 8517-8534.
Schlunegger, M.P, et al. (1992) An unusual feature revealed by the crystal structure at 2.2 A resolution of human transforming growth factor-beta 2. Nature. 358: 430-434.
Mittl, P.R, et al. (1996). The crystal structure of TGF-beta 3 and comparison to TGF-beta 2: implications for receptor binding. Protein Sci. 5: 1261-1271.
Kaartinen V, et al. (1995) ). Abnormal lung development and cleft palate in mice lacking TGF-beta 3 indicates defects of epithelial-mesenchymal interaction. Nat Genet. 11 (4): 415–21.