Characterization of R-ras3/m-ras null mice reveals a potential role in trophic factor signaling.
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.
Nuñez Rodriguez
Nelson
N
Department of Oncological Sciences, The Mount Sinai School of Medicine, New York, New York 10029, USA.
Lee
Ivy N L
IN
Banno
Asoka
A
Qiao
Hui F
HF
Qiao
Rui F
RF
Yao
Zhong
Z
Hoang
Thuong
T
Kimmelman
Alec C
AC
Chan
Andrew M-L
AM
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006133:Growth Substances / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020559:Monomeric GTP-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010770:Phosphotransferases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000187:drug effects*; D018631:ras Proteins
D006133:Growth Substances; D012333:RNA, Messenger; D010770:Phosphotransferases; C109418:Mras protein, mouse; D020559:Monomeric GTP-Binding Proteins; D018631:ras Proteins