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Transforming growth factor beta superfamily

Protein family

Protein family

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. 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:

  • The TGF-β subfamily
  • The bone morphogenetic proteins and the growth differentiation factors
  • The activin and inhibin subfamilies
  • The left-right determination factors
  • A group encompassing various divergent members

Transforming growth factor-beta (TGF-beta) 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.

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, 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 | +------------------------------------------|+ | || xxxxcxxxxxCcxxxxxxxxxxxxxxxxxxCxxCxxxxxxxxxxxxxxxxxxxCCxxxxxxxxxxxxxxxxxxxCxCx | | | | | | +------+ +--|----------------------------------------+ | +------------------------------------------+

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;

References

References

  1. (July 1992). "An unusual feature revealed by the crystal structure at 2.2 A resolution of human transforming growth factor-beta 2". Nature.
  2. (June 1983). "Transforming growth factor-beta in human platelets. Identification of a major storage site, purification, and characterization". J. Biol. Chem..
  3. (May 2004). "Transforming growth factor-beta-related proteins: an ancestral and widespread superfamily of cytokines in metazoans". Dev. Comp. Immunol..
  4. Burt DW. (April 1992). "Evolutionary grouping of the transforming growth factor-beta superfamily". Biochem. Biophys. Res. Commun..
  5. (1994). "Evolution of the transforming growth factor-beta superfamily". Prog. Growth Factor Res..
  6. (1990). "Peptide growth factors and their receptors". Springer-Verlag.
  7. (July 1992). "Crystal structure of transforming growth factor-beta 2: an unusual fold for the superfamily". Science.
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developmental-genes-and-proteins tgfβ-domain protein-domains membrane-proteins protein-families
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