Inner nuclear membrane and regulation of Smad-mediated signaling.
Smads mediate signal transduction by cytokines of the transforming growth factor-beta family. Recent data show that intrinsic and extrinsic proteins of the inner nuclear membrane affect the activities of Smads. MAN1, an integral protein of the inner nuclear membrane, binds to receptor-regulated Smads and antagonizes signaling by transforming growth factor-beta, activin and bone morphogenic protein. Lamins A and C, extrinsic intermediate filament proteins of the inner nuclear membrane that are mutated in several human diseases, appear to regulate phosphorylation of Smads. These data demonstrate that proteins within and associated with the inner nuclear membrane lipid bilayer regulate signal transduction pathways involved in numerous developmental, physiological and pathophysiological processes.
Department of Medicine, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, 10th Floor, Room 508, New York, NY 10032, USA. hjw14@columbia.edu
Howard J
HJ
Worman
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D002468:Cell Physiological Phenomena; D005246:Feedback / Q000502:physiology; D006801:Humans; D009685:Nuclear Envelope / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D051785:Smad Proteins / Q000378:metabolism*
D009687:Nuclear Proteins; D051785:Smad Proteins