GTPase

Biology

Signal transduction

Cell biology

Cell membrane

Biochemistry

Membrane protein

Receptor

Signal transducing adaptor protein

Membrane

Effector

Chemistry

Endocytosis

Nature Structural & Molecular Biology

Analyses in supported lipid bilayers and in cells shed light on the roles of multiple SOS-membrane interactions in SOS's membrane recruitment and association, processive activation of Ras and signal attenuation. SOS is a key activator of the small GTPase Ras. In cells, SOS-Ras signaling is thought to be initiated predominantly by membrane recruitment of SOS via the adaptor Grb2 and balanced by rapidly reversible Grb2-SOS binding kinetics. However, SOS has multiple protein and lipid interactions that provide linkage to the membrane. In reconstituted-membrane experiments, these Grb2-independent interactions were sufficient to retain human SOS on the membrane for many minutes, during which a single SOS molecule could processively activate thousands of Ras molecules. These observations raised questions concerning how receptors maintain control of SOS in cells and how membrane-recruited SOS is ultimately released. We addressed these questions in quantitative assays of reconstituted SOS-deficient chicken B-cell sig...

One-way membrane trafficking of SOS in receptor-triggered Ras activation