| Title: | Activation of the phosphatidylinositol 3-kinase Vps34 by a G protein alpha subunit at the endosome |
| Author(s): | Slessareva JE; Routt SM; Temple B; Bankaitis VA; Dohlman HG; |
| Address: | "Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA" |
| DOI: | 10.1016/j.cell.2006.04.045 |
| ISSN/ISBN: | 0092-8674 (Print) 0092-8674 (Linking) |
| Abstract: | "In the yeast Saccharomyces cerevisiae, the G protein beta gamma subunits are essential for pheromone signaling. The Galpha subunit Gpa1 can also promote signaling, but the effectors in this pathway are not well characterized. To identify candidate Gpa1 effectors, we expressed the constitutively active Gpa1(Q323L) mutant in each of nearly 5000 gene-deletion strains and measured mating-specific responses. Our analysis reveals a requirement for both the catalytic (Vps34) and regulatory (Vps15) subunits of the sole phosphatidylinositol 3-kinase in yeast. We demonstrate that Gpa1 is present at endosomes, where it interacts directly with both Vps34 and Vps15 and stimulates increased production of phosphatidylinositol 3-phosphate. Notably, Vps15 binds to GDP-bound Gpa1 and is predicted to have a seven-WD repeat structure similar to that of known G protein beta subunits. These findings reveal two new components of the pheromone signaling pathway. More remarkably, these proteins appear to comprise a preformed effector-G beta subunit assembly and function at the endosome rather than at the plasma membrane" |
| Keywords: | Binding Sites/physiology Endosomal Sorting Complexes Required for Transport Endosomes/*enzymology/genetics Enzyme Activation/*physiology GTP-Binding Protein alpha Subunits/genetics/*metabolism Guanosine Diphosphate/metabolism Mutation/physiology Pheromone; |
| Notes: | "MedlineSlessareva, Janna E Routt, Sheri M Temple, Brenda Bankaitis, Vytas A Dohlman, Henrik G eng P01 GM065533/GM/NIGMS NIH HHS/ P01 GM65533/GM/NIGMS NIH HHS/ R01 GM44530/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural 2006/07/15 Cell. 2006 Jul 14; 126(1):191-203. doi: 10.1016/j.cell.2006.04.045" |
