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Publication : Involvement of a small GTP-binding protein (G protein) regulator, small G protein GDP dissociation stimulator, in antiapoptotic cell survival signaling.

First Author  Takakura A Year  2000
Journal  Mol Biol Cell Volume  11
Issue  5 Pages  1875-86
PubMed ID  10793158 Mgi Jnum  J:62244
Mgi Id  MGI:1858633 Doi  10.1091/mbc.11.5.1875
Citation  Takakura A, et al. (2000) Involvement of a small GTP-binding protein (G protein) regulator, small G protein GDP dissociation stimulator, in antiapoptotic cell survival signaling. Mol Biol Cell 11(5):1875-86
abstractText  Small GTP-binding protein GDP dissociation stimulator (Smg GDS) regulates GDP/GTP exchange reaction of Ki-Ras and the Rho and Rap1 family members and inhibits their binding to membranes. In fibroblasts, Smg GDS shows mitogenic and transforming activities in cooperation with Ki-Ras. However, the physiological function of Smg GDS remains unknown. Here we show that mice lacking Smg GDS died of heart failure shortly after birth, not resulting from developmental heart defects but from enhanced apoptosis of cardiomyocytes triggered by cardiovascular overload. Furthermore, neonatal thymocytes and developing neuronal cells underwent apoptotic cell death. Smg GDS-/- thymocytes were susceptible to apoptotic inducers, such as etoposide and UV irradiation. Smg GDS-/- thymocytes were protected from etoposide-induced cell death by ex vivo transduction of the Smg GDS cDNA. These phenotypes partly coincide with those observed in Ki-Ras-deficient mice, suggesting that Smg GDS is involved in antiapoptotic cell survival signaling through Ki-Ras.
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