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Ras-dependent activation of the small GTPase Ral
R M Wolthuis1, F Zwartkruis, T C Moen
1Laboratory for Physiological Chemistry, Utrecht University, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands.
Current Biology : CB
|May 30, 1998
Summary
Growth factors rapidly activate the small GTPase Ral, a process dependent on Ras activation. This finding clarifies Ral
Area of Science:
- Cellular signaling pathways
- Molecular biology
- Oncogenesis
Background:
- The small GTPase Ral is implicated in DNA synthesis and oncogenic transformation.
- Ral guanine nucleotide exchange factors (Ral GEFs) bind to GTP-bound Ras-like GTPases.
- The role of growth factors in Ral activation and the specific GTPase involved remained unclear.
Purpose of the Study:
- To investigate whether growth factors induce Ral activation.
- To identify the small GTPase responsible for mediating growth factor-induced Ral activation.
Main Methods:
- Stimulation of various growth factor receptors (receptor tyrosine kinases, serpentine receptors).
- Assessing Ral activation.
- Assessing Ras activation.
- Utilizing dominant-negative Ras to inhibit Ral activation.
Main Results:
- Growth factor receptor stimulation leads to rapid Ral activation.
- Ral activation correlates with Ras activation.
- Dominant-negative Ras completely blocks insulin and EGF-induced Ral activation.
Conclusions:
- Ral activation is a direct downstream consequence of growth-factor-induced Ras activation.
- Ras is the key small GTPase mediating Ral activation by growth factors.