Membrane localization of the small GTP-binding protein Ras is essential for its function. Upon activation, Ras binds to the serine-threonine kinase Raf-1. Inouye et al. suggest that Ras must dimerize at the membrane to activate Raf-1. Purified, GTP-bound Ras that was incorporated into liposomes formed dimers that activated Raf-1 in the absence of other membrane proteins. This effect did not occur in the absence of liposomes. Ras fusion proteins that formed dimers could bypass incorporation into liposomes for Raf-1 activation, and Ras fusion proteins induced to dimerize in intact cells also activated Raf-1. It remains unclear how Ras might dimerize in the membrane.
Inouye, K., Mizutani, S., Koide, H., and Kaziro, Y. (2000) Formation of the Ras dimer is essential for Raf-1 activation. J. Biol. Chem. 275: 3737-3740. [Abstract] [Full Text]
