Killer K-Ras

K-Ras resides at the plasma membrane (PM) where it promotes cell survival and proliferation. Now, Trever Bivona, Mark Philips (New York University, New York, NY), and colleagues find that fluorescent K-Ras moves to internal cell membranes within a few minutes after activating protein kinase C (PKC), with deadly consequences.

Philips' group happened to stimulate GFP-labeled T cells for an unrelated experiment. “Before our eyes, K-Ras shot off the membrane and into the cell interior,” says Philips. K-Ras is attached peripherally to the PM by a farnesyl lipid group and an adjacent polybasic sequence. The team hypothesized that phosphorylation by PKC within the polybasic region acted like a switch, neutralizing the positive charge and releasing K-Ras from the PM. Indeed, blocking this serine-181 phosphorylation by PKC prevented K-Ras internalization.

A phosphate-mimicking Glu-181 mutant gave another shocking...