Characterization of R-ras3/m-ras null mice reveals a potential role in trophic factor signaling |
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Authors: | Nuñez Rodriguez Nelson Lee Ivy N L Banno Asoka Qiao Hui F Qiao Rui F Yao Zhong Hoang Thuong Kimmelman Alec C Chan Andrew M-L |
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Affiliation: | Department of Oncological Sciences, The Mount Sinai School of Medicine, New York, New York 10029, USA. |
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Abstract: | R-Ras3/M-Ras is a member of the RAS superfamily of small-molecular-weight GTP-binding proteins. Previous studies have demonstrated high levels of expression in several regions of the central nervous system, and a constitutively active form of M-Ras promotes cytoskeletal reorganization, cellular transformation, survival, and differentiation. However, the physiological functions of M-Ras during embryogenesis and postnatal development have not been elucidated. By using a specific M-Ras antibody, we demonstrated a high level of M-Ras expression in astrocytes, in addition to neurons. Endogenous M-Ras was activated by several trophic factors in astrocytes, including epidermal growth factor (EGF), basic fibroblast growth factor, and hepatocyte growth factor. Interestingly, M-Ras activation by EGF was more sustained compared to prototypic Ras. A mouse strain deficient in M-Ras was generated to investigate its role in development. M-Ras null mice appeared phenotypically normal, and there was a lack of detectable morphological and neurological defects. In addition, primary astrocytes derived from Mras(-/-) mice did not appear to display substantial alterations in the activation of both the mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways in response to trophic factors. |
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