SMADs: mediators and regulators of TGF-beta signaling.
The discovery of SMAD proteins has allowed the delineation of a mechanism by which TGF-beta and related growth factors convey their signals from membrane receptors all the way into the nucleus. SMADs are directly phosphorylated and activated by the receptors and then form heteromeric SMAD-SMAD complexes that move into the nucleus where they orchestrate transcriptional responses. In rapid succession, recent reports have identified different modes of SMAD regulation by phosphorylation and have defined the SMAD domains that mediate SMAD interactions, binding to DNA or transcriptional activation. The recent discovery of antagonistic SMADs and regulatory crosstalk with Ras/MAP-kinase pathways add to our rapidly expanding understanding of this major regulatory network.
Kretzschmar
M
M
Cell Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Massagué
J
J
D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D011956:Receptors, Cell Surface / Q000378:metabolism; D012097:Repressor Proteins; D015398:Signal Transduction; D051785:Smad Proteins; D015534:Trans-Activators; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C079439:MXD1 protein, human; D011956:Receptors, Cell Surface; D012097:Repressor Proteins; D051785:Smad Proteins; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D017871:Calcium-Calmodulin-Dependent Protein Kinases