PMID- 12221133 OWN - NLM STAT- MEDLINE DCOM- 20030312 LR - 20181113 IS - 1059-1524 (Print) IS - 1059-1524 (Linking) VI - 13 IP - 9 DP - 2002 Sep TI - Membrane trafficking of heterotrimeric G proteins via the endoplasmic reticulum and Golgi. PG - 3294-302 AB - Membrane targeting of G-protein alphabetagamma heterotrimers was investigated in live cells by use of Galpha and Ggamma subunits tagged with spectral mutants of green fluorescent protein. Unlike Ras proteins, Gbetagamma contains a single targeting signal, the CAAX motif, which directed the dimer to the endoplasmic reticulum. Endomembrane localization of farnesylated Ggamma(1), but not geranylgeranylated Ggamma(2), required carboxyl methylation. Targeting of the heterotrimer to the plasma membrane (PM) required coexpression of all three subunits, combining the CAAX motif of Ggamma with the fatty acyl modifications of Galpha. Galpha associated with Gbetagamma on the Golgi and palmitoylation of Galpha was required for translocation of the heterotrimer to the PM. Thus, two separate signals, analogous to the dual-signal targeting mechanism of Ras proteins, cooperate to target heterotrimeric G proteins to the PM via the endomembrane. FAU - Michaelson, David AU - Michaelson D AD - Department of Medicine, Cell Biology and Pharmacology, NYU School of Medicine, 10016, USA. FAU - Ahearn, Ian AU - Ahearn I FAU - Bergo, Martin AU - Bergo M FAU - Young, Stephen AU - Young S FAU - Philips, Mark AU - Philips M LA - eng GR - CA-09161/CA/NCI NIH HHS/United States GR - T32 CA009161/CA/NCI NIH HHS/United States GR - M01 RR000096/RR/NCRR NIH HHS/United States GR - GM-55279/GM/NIGMS NIH HHS/United States GR - R29 AI036224/AI/NIAID NIH HHS/United States GR - R01 GM055279/GM/NIGMS NIH HHS/United States GR - AI-36224/AI/NIAID NIH HHS/United States GR - R01 AI036224/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Mol Biol Cell JT - Molecular biology of the cell JID - 9201390 RN - 0 (Luminescent Proteins) RN - 0 (Recombinant Fusion Proteins) RN - 147336-22-9 (Green Fluorescent Proteins) RN - EC 3.6.1.- (GTP-Binding Proteins) SB - IM MH - Amino Acid Motifs MH - Animals MH - Biological Transport MH - COS Cells MH - Cell Line MH - Cell Membrane/metabolism MH - Dogs MH - Endoplasmic Reticulum/*metabolism MH - GTP-Binding Proteins/*metabolism MH - Golgi Apparatus/*metabolism MH - Green Fluorescent Proteins MH - Humans MH - Luminescent Proteins/metabolism MH - Microscopy, Fluorescence MH - Models, Biological MH - Plasmids/metabolism MH - Protein Binding MH - Protein Prenylation MH - Protein Structure, Tertiary MH - Recombinant Fusion Proteins/metabolism MH - Signal Transduction PMC - PMC124159 EDAT- 2002/09/11 10:00 MHDA- 2003/03/13 04:00 PMCR- 2002/11/01 CRDT- 2002/09/11 10:00 PHST- 2002/09/11 10:00 [pubmed] PHST- 2003/03/13 04:00 [medline] PHST- 2002/09/11 10:00 [entrez] PHST- 2002/11/01 00:00 [pmc-release] AID - 1960 [pii] AID - 10.1091/mbc.e02-02-0095 [doi] PST - ppublish SO - Mol Biol Cell. 2002 Sep;13(9):3294-302. doi: 10.1091/mbc.e02-02-0095.