TGF-beta signaling, Smads, and tumor suppressors.
The transforming growth factor-beta (TGF-beta) superfamily is used throughout animal development for regulating the growth and patterning of many tissue types. During the past few years, rapid progress has been made in deciphering how TGF-beta signals are transduced from outside the cell to the nucleus. This progress is based on biochemical studies in vertebrate systems and a combination of genetic studies in Drosophila and Caenorhabditis elegans. These studies have identified a novel family of signaling proteins, the Smad family. Smads can act positively and be phosphorylated by TGF-beta-like receptors or can act negatively and prevent activation of the positively acting group. The positively acting Smads translocate to the nucleus, bind DNA, and act as transcriptional activators. Thus, genetic and biochemical studies suggest a very simple signaling pathway, in which Smads are the primary downstream participant.
Waksman Institute, Department of Molecular Biology and Biochemistry, Cancer Institute of New Jersey, Rutgers University, Piscataway 08855-0759, USA. padgett@mbcl.rutgers.edu
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D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology; D004330:Drosophila / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D008957:Models, Genetic; D010750:Phosphoproteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology*; D014714:Vertebrates
D004268:DNA-Binding Proteins; D010750:Phosphoproteins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta