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The kelch proteins Gpb1 and Gpb2 inhibit Ras activity via association with the yeast RasGAP neurofibromin homologs Ira1 and Ira2.
- Source :
-
Molecular cell [Mol Cell] 2006 Jun 23; Vol. 22 (6), pp. 819-830. - Publication Year :
- 2006
-
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.
- Subjects :
- Adaptor Proteins, Signal Transducing
Adenylyl Cyclases genetics
Adenylyl Cyclases metabolism
Cell Transformation, Neoplastic genetics
Cell Transformation, Neoplastic metabolism
Cyclic AMP-Dependent Protein Kinases
GTPase-Activating Proteins
Gene Deletion
Humans
Neurofibromatosis 1 genetics
Neurofibromatosis 1 metabolism
Neurofibromin 1 genetics
Neurofibromin 1 metabolism
Protein Binding genetics
Protein Serine-Threonine Kinases metabolism
Protein Structure, Tertiary genetics
Repressor Proteins genetics
Saccharomyces cerevisiae cytology
Saccharomyces cerevisiae genetics
Saccharomyces cerevisiae Proteins genetics
Sequence Homology, Amino Acid
ras Proteins genetics
Repressor Proteins metabolism
Saccharomyces cerevisiae metabolism
Saccharomyces cerevisiae Proteins metabolism
Signal Transduction
ras Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1097-2765
- Volume :
- 22
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Molecular cell
- Publication Type :
- Academic Journal
- Accession number :
- 16793550
- Full Text :
- https://doi.org/10.1016/j.molcel.2006.05.011