Decoding the quantitative nature of TGF-beta/Smad signaling.
How transforming growth factor-beta (TGF-beta) signaling elicits diverse cell responses remains elusive, despite the major molecular components of the pathway being known. We contend that understanding TGF-beta biology requires mathematical models to decipher the quantitative nature of TGF-beta/Smad signaling and to account for its complexity. Here, we review mathematical models of TGF-beta superfamily signaling that predict how robustness is achieved in bone-morphogenetic-protein signaling in the Drosophila embryo, how changes in receptor-trafficking dynamics can be exploited by cancer cells and how the basic mechanisms of TGF-beta/Smad signaling conspire to promote Smad accumulation in the nucleus. These studies demonstrate the power of mathematical modeling for understanding TGF-beta biology.
Clarke
David C
DC
Department of Chemistry and Biochemistry, University of Colorado-Boulder, Boulder, CO 80309-0215, USA.
Liu
Xuedong
X
D000818:Animals; D019521:Body Patterning; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D019281:Dimerization; D004330:Drosophila / Q000196:embryology / Q000378:metabolism; D008024:Ligands; D009369:Neoplasms / Q000378:metabolism; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D019485:Bone Morphogenetic Proteins; D008024:Ligands; D051785:Smad Proteins; D016212:Transforming Growth Factor beta