Transforming growth factor beta superfamily explained

The transforming growth factor beta (TGF-β) superfamily is a large group of structurally related cell regulatory proteins that was named after its first member, TGF-β1, originally described in 1983.[1] They interact with TGF-beta receptors.

Many proteins have since been described as members of the TGF-β superfamily in a variety of species, including invertebrates as well as vertebrates and categorized into 23 distinct gene types that fall into four major subfamilies:[2] [3] [4]

Transforming growth factor-beta (TGF-beta)[5] is a multifunctional peptide that controls proliferation, differentiation and other functions in many cell types. TGF-beta-1 is a peptide of 112 amino acid residues derived by proteolytic cleavage from the C-terminal of a precursor protein. These proteins interact with a conserved family of cell surface serine/threonine-specific protein kinase receptors, and generate intracellular signals using a conserved family of proteins called SMADs. They play fundamental roles in the regulation of basic biological processes such as growth, development, tissue homeostasis and regulation of the immune system.[2]

Structure

Proteins from the TGF-beta superfamily are only active as homo- or heterodimer; the two chains being linked by a single disulfide bond. From X-ray studies of TGF-beta-2,[6] it is known that all the other cysteines are involved in intrachain disulfide bonds. As shown in the following schematic representation, there are four disulfide bonds in the TGF-beta's and in inhibin beta chains, while the other members of this superfamily lack the first bond.

interchain | +------------------------------------------|+ | || | | | | | | +------+ +--|----------------------------------------+ | +------------------------------------------+

where 'C' denotes a conserved cysteine involved in a disulfide bond.

Examples

Human genes encoding proteins that contain this domain include:

AMH

ARTN; BMP2; BMP3; BMP4; BMP5; BMP6; BMP7; BMP8A; BMP8B; BMP10; BMP15; GDF1
  • GDF2; GDF3; GDF5; GDF6; GDF7; GDF9; GDF10; GDF11; GDF15; GDNF; INHA; INHBA; INHBB; INHBC; INHBE; LEFTY1; LEFTY2;MSTN
  • NODAL; NRTN; PSPN; TGFB1; TGFB2; TGFB3;
  • Notes and References

    1. Assoian RK, Komoriya A, Meyers CA, Miller DM, Sporn MB . Transforming growth factor-beta in human platelets. Identification of a major storage site, purification, and characterization . J. Biol. Chem. . 258 . 11 . 7155–60 . June 1983 . 10.1016/S0021-9258(18)32345-7 . 6602130 . free .
    2. Herpin A, Lelong C, Favrel P . Transforming growth factor-beta-related proteins: an ancestral and widespread superfamily of cytokines in metazoans . Dev. Comp. Immunol. . 28 . 5 . 461–85 . May 2004 . 15062644 . 10.1016/j.dci.2003.09.007 .
    3. Burt DW . Evolutionary grouping of the transforming growth factor-beta superfamily . Biochem. Biophys. Res. Commun. . 184 . 2 . 590–5 . April 1992 . 1575734 . 10.1016/0006-291X(92)90630-4 .
    4. Burt DW, Law AS . Evolution of the transforming growth factor-beta superfamily . Prog. Growth Factor Res. . 5 . 1 . 99–118 . 1994 . 8199356 . 10.1016/0955-2235(94)90020-5 . 20.500.11820/50fc2d69-c411-4835-9cd9-36bf4144bae4 . 41326578 . free .
    5. Book: Roberts AB, Sporn MB . Peptide growth factors and their receptors . Springer-Verlag . Berlin . 1990 . 3-540-51184-9 . registration .
    6. Daopin S, Piez KA, Ogawa Y, Davies DR . Crystal structure of transforming growth factor-beta 2: an unusual fold for the superfamily . Science . 257 . 5068 . 369–73 . July 1992 . 1631557 . 10.1126/science.1631557 . 1992Sci...257..369D .