Scaffold proteins dictate Rho GTPase-signaling specificity.

Given the numerous mechanisms that regulate the activity of Rho GTPases and the multiple effectors for Rho proteins, how is specificity achieved when transducing signals via Rho GTPase-regulated molecular networks? The finding that the scaffold protein hCNK1 links Rho guanine-nucleotide-exchange factors and Rho to JNK (c-Jun N-terminal kinase), while limiting stress-fiber formation and serum-response-factor activation, suggests that scaffold proteins govern the selection of signal outputs, thus helping to solve the Rho GTPase-signaling puzzle.