Prenylated Rab Acceptor Protein Is a Receptor for Prenylated Small GTPases

• Published in: The Journal of biological chemistry Vol. 276; no. 30; pp. 28219 - 28225
• Main Authors: Figueroa, C, Taylor, J, Vojtek, A B
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 27.07.2001
• Subjects: Animals; Carrier Proteins; Cell Line; Cell Membrane - metabolism; Conserved Sequence; COS Cells; Evolution, Molecular; Fungal Proteins - metabolism; Glutathione Transferase - metabolism; Golgi Apparatus - metabolism; Green Fluorescent Proteins; GTP Phosphohydrolases - metabolism; GTP-Binding Proteins; Humans; Luminescent Proteins - metabolism; Membrane Proteins; Models, Biological; Multigene Family; Plasmids - metabolism; Protein Binding; Protein Prenylation; Protein Processing, Post-Translational; Proto-Oncogene Proteins p21(ras) - metabolism; rab GTP-Binding Proteins - metabolism; Receptors, Cell Surface; Recombinant Fusion Proteins - metabolism; rhoA GTP-Binding Protein - metabolism; Transfection; Vesicular Transport Proteins
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M101763200

Localization of Ras and Ras-like proteins to the correct subcellular compartment is essential for these proteins to mediate their biological effects. Many members of the Ras superfamily (Ha-Ras, N-Ras, TC21, and RhoA) are prenylated in the cytoplasm and then transit through the endomembrane system on their way to the plasma membrane. The proteins that aid in the trafficking of the small GTPases have not been well characterized. We report here that prenylated Rab acceptor protein (PRA1), which others previously identified as a prenylation-dependent receptor for Rab proteins, also interacts with Ha-Ras, RhoA, TC21, and Rap1a. The interaction of these small GTPases with PRA1 requires their post-translational modification by prenylation. The prenylation-dependent association of PRA1 with multiple GTPases is conserved in evolution; the yeast PRA1 protein associates with both Ha-Ras and RhoA. Earlier studies reported the presence of PRA1 in the Golgi, and we show here that PRA1 co-localizes with Ha-Ras and RhoA in the Golgi compartment. We suggest that PRA1 acts as an escort protein for small GTPases by binding to the hydrophobic isoprenoid moieties of the small GTPases and facilitates their trafficking through the endomembrane system.