Sci. Signal., 18 December 2012
Another Helping Hand to the MembraneGrowth factor stimulation activates the mitogen-activated protein kinase module, in which Raf activates MEK, which in turn activates ERK. Kinase suppressor of Ras-1 (KSR-1) requires a phospholipid-binding atypical C1 domain to associate with the plasma membrane to promote assembly of this module. Koveal et al. identified a sterile α motif (SAM) adjacent to a coiled coil (CC) domain in KSR-1. Structural and biochemical analysis of just the CC and SAM regions showed that CC-SAM formed a single, structural module. CC-SAM bound directly to micelles and bicelles in vitro and was targeted to the plasma membrane in growth factor–treated cells. Structure-based point mutations in helix α3 of the CC motif prevented the binding of CC-SAM to micelles and bicelles. Full-length KSR-1 with these mutations did not localize to the plasma membrane or interact with B-Raf when expressed in growth factor–treated cells. Thus, KSR-1 requires the atypical C1 and CC-SAM domains to associate with the plasma membrane.
Citation: D. Koveal, N. Schuh-Nuhfer, D. Ritt, R. Page, D. K. Morrison, W. Peti, A CC-SAM, for Coiled Coil–Sterile α Motif, Domain Targets the Scaffold KSR-1 to Specific Sites in the Plasma Membrane. Sci. Signal. 5, ra94 (2012).
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