Identification of a novel prenyl and palmitoyl modification at the CaaX motif of Cdc42 that regulates RhoGDI binding.

摘要: Membrane localization of Rho GTPases is essential for their biological functions and dictated in part by a series posttranslational modifications at carboxyl-terminal CaaX motif: prenylation cysteine, proteolysis the aaX tripeptide, carboxymethylation. The fidelity variability these processing steps are uncertain. brain-specific splice variant Cdc42 (bCdc42) terminates CCIF sequence. Here we show that brain undergoes two different types modification: classical or novel tandem palmitoylation CCaX cysteines. In dual lipidation pathway, bCdc42 was prenylated, but it bypassed carboxymethylation to undergo modification with palmitate second cysteine. alternative postprenylation fates were conserved RalA RalB phosphatase PRL-3, proteins terminating motif. differentially modified forms displayed functional differences. Prenylated palmitoylated did not interact RhoGDIα enriched plasma membrane relative classically processed form. prenylated motif endoproteolysis methylation expands diversity signaling enables another level regulation through reversible palmitate.