Transforming growth factor beta family

From Wikipedia, the free encyclopedia
Jump to navigation Jump to search
Transforming growth factor beta like domain
PDB 1tfg EBI.jpg
Structure of human transforming growth factor-beta 2.[1]
Identifiers
Symbol TGF_beta
Pfam PF00019
InterPro IPR001839
PROSITE PDOC00223
SCOP 1tfg
SUPERFAMILY 1tfg

The transforming growth factor beta (TGF-β) family is a large group of structurally related cell regulatory proteins that was named after its first member, TGF-β1, originally described in 1983.[2]. They interact with TGF-beta receptors.

Many proteins have since been described as members of the TGF-β family in a variety of species, including invertebrates as well as vertebrates and categorized into 23 distinct gene types that fall into four major subfamilies:[3][4][5]

Transforming growth factor-beta (TGF-beta)[6] 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.[3]

Structure[edit]

Proteins from the TGF-beta family 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,[7] 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 family lack the first bond.

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

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

Examples[edit]

Human genes encoding proteins that contain this domain include:

AMH; ARTN; BMP10; BMP15; BMP2; BMP3; BMP4; BMP5; BMP6; BMP7; BMP8A; BMP8B; GDF1; GDF10; GDF11; GDF15; GDF2; GDF3; GDF3A; GDF5; GDF6; GDF7; GDF8; GDF9; GDNF; INHA; INHBA; INHBB; INHBC; INHBE; LEFTY1; LEFTY2; MSTN; NODAL; NRTN; PSPN; TGFB1; TGFB2; TGFB3;

References[edit]

  1. ^ Schlunegger MP, Grütter MG (July 1992). "An unusual feature revealed by the crystal structure at 2.2 A resolution of human transforming growth factor-beta 2". Nature. 358 (6385): 430–4. doi:10.1038/358430a0. PMID 1641027.
  2. ^ Assoian RK, Komoriya A, Meyers CA, Miller DM, Sporn MB (June 1983). "Transforming growth factor-beta in human platelets. Identification of a major storage site, purification, and characterization". J. Biol. Chem. 258 (11): 7155–60. PMID 6602130.
  3. ^ a b Herpin A, Lelong C, Favrel P (May 2004). "Transforming growth factor-beta-related proteins: an ancestral and widespread superfamily of cytokines in metazoans". Dev. Comp. Immunol. 28 (5): 461–85. doi:10.1016/j.dci.2003.09.007. PMID 15062644.
  4. ^ Burt DW (April 1992). "Evolutionary grouping of the transforming growth factor-beta superfamily". Biochem. Biophys. Res. Commun. 184 (2): 590–5. doi:10.1016/0006-291X(92)90630-4. PMID 1575734.
  5. ^ Burt DW, Law AS (1994). "Evolution of the transforming growth factor-beta superfamily". Prog. Growth Factor Res. 5 (1): 99–118. doi:10.1016/0955-2235(94)90020-5. PMID 8199356.
  6. ^ Roberts AB, Sporn MB (1990). Peptide growth factors and their receptors. Berlin: Springer-Verlag. ISBN 3-540-51184-9.
  7. ^ Daopin S, Piez KA, Ogawa Y, Davies DR (July 1992). "Crystal structure of transforming growth factor-beta 2: an unusual fold for the superfamily". Science. 257 (5068): 369–73. doi:10.1126/science.1631557. PMID 1631557.