Signal transduction of the TGF-beta superfamily by Smad proteins.
Members of the TGF-beta superfamily regulate the growth and differentiation of various types of cells. Smads are recently identified proteins that mediate intracellular signaling of the TGF-beta superfamily. Smads are grouped into three classes depending on their structure and functions. R-Smads are phosphorylated by type I serine-threonine kinase receptors for TGF-beta superfamily members. R-Smads then associate with Co-Smads. Smad4 is the only vertebrate Co-Smad identified thus far, and is required for the signaling pathways of different ligands. The heteromeric Smad complex translocates into the nucleus, where it activates target genes. Anti-Smads inhibit signaling by R-Smads and Co-Smads. Smads bind to DNA directly or indirectly via other DNA binding proteins. R-Smads interact with transcriptional coactivators, and have intrinsic transactivation activity. Elucidation of the functions of Smads will provide the framework for research on TGF-beta superfamily signaling.
Kawabata
M
M
Department of Biochemistry, The Cancer Institute, Japanese Foundation for Cancer Research (JFCR), Toshima-ku, Tokyo 170-8455, Japan. mkawabat-ind@umin.u-tokyo.ac.jp
Miyazono
K
K
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins; D005799:Genes, Dominant; D006801:Humans; D015398:Signal Transduction; D051785:Smad Proteins; D051899:Smad2 Protein; D051900:Smad3 Protein; D015534:Trans-Activators / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C112506:MAD protein, Drosophila; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D051785:Smad Proteins; D051899:Smad2 Protein; D051900:Smad3 Protein; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta