Philips/Macmillan

Ras (white) is activated on both the plasma membrane and the Golgi (left to right).

The plasma membrane has been considered the exclusive platform from which Ras GTPases signal. But recent results from Vi Chiu, Trever Bivona, Mark Philips (New York University School of Medicine, New York, NY), and colleagues demonstrate that Ras proteins are also active on internal membranes.

Ras GTPases are molecular switches that transduce mitogenic signals by activating downstream effectors, particularly in the MAPK pathway, when GTP is bound. Previous results have led to the belief that Ras is only active when bound to the cytosolic face of the plasma membrane. Several isoforms of human Ras exist, including K-Ras, N-Ras, and H-Ras, but the biological need for this diversity has been unclear. “If all three lead to MAPK activation, why have so many different isoforms?” says Philips. It has been hypothesized...

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