Two major Smad pathways in TGF-beta superfamily signalling.
Members of the transforming growth factor-beta (TGF-beta) superfamily bind to two different serine/threonine kinase receptors, i.e. type I and type II receptors. Upon ligand binding, type I receptors specifically activate intracellular Smad proteins. R-Smads are direct substrates of type I receptors; Smads 2 and 3 are specifically activated by activin/nodal and TGF-beta type I receptors, whereas Smads 1, 5 and 8 are activated by BMP type I receptors. Nearly 30 proteins have been identified as members of the TGF-beta superfamily in mammals, and can be classified based on whether they activate activin/TGF-beta-specific R-Smads (AR-Smads) or BMP-specific R-Smads (BR-Smads). R-Smads form complexes with Co-Smads and translocate into the nucleus, where they regulate the transcription of target genes. AR-Smads bind to various proteins, including transcription factors and transcriptional co-activators or co-repressors, whereas BR-Smads interact with other proteins less efficiently than AR-Smads. Id proteins are induced by BR-Smads, and play important roles in exhibiting some biological effects of BMPs. Understanding the mechanisms of TGF-beta superfamily signalling is thus important for the development of new ways to treat various clinical diseases in which TGF-beta superfamily signalling is involved.
Miyazawa
Keiji
K
Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Japan.
Shinozaki
Masahiko
M
Hara
Takane
T
Furuya
Toshio
T
Miyazono
Kohei
K
D000818:Animals; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D005810:Multigene Family; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D051785:Smad Proteins; D015534:Trans-Activators / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D004268:DNA-Binding Proteins; D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D015534:Trans-Activators; D016212:Transforming Growth Factor beta