The BioGRID | PUBLICATION VIEW

	Mol. Cell Jun (2006); 22(6):819-30
The kelch proteins Gpb1 and Gpb2 inhibit Ras activity via association with the yeast RasGAP neurofibromin homologs Ira1 and Ira2-
Harashima T, Anderson S, Yates JR, Heitman J
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA-
Abstract: The G protein-coupled receptor Gpr1 and associated Galpha subunit Gpa2 govern dimorphic transitions in response to extracellular nutrients by signaling coordinately with Ras to activate adenylyl cyclase in the yeast Saccharomyces cerevisiae- Gpa2 forms a protein complex with the kelch Gbeta mimic subunits Gpb1-2, and previous studies demonstrate that Gpb1-2 negatively control cAMP-PKA signaling via Gpa2 and an unknown second target- Here, we define these targets of Gpb1-2 as the yeast neurofibromin homologs Ira1 and Ira2, which function as GTPase activating proteins of Ras- Gpb1-2 bind to a conserved C-terminal domain of Ira1-2, and loss of Gpb1-2 results in a destabilization of Ira1 and Ira2, leading to elevated levels of Ras2-GTP and unbridled cAMP-PKA signaling- Because the Gpb1-2 binding domain on Ira1-2 is conserved in the human neurofibromin protein, an analogous signaling network may contribute to the neoplastic development of neurofibromatosis type 1-
[PUBMED: 16793550]