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The kelch proteins Gpb1 and Gpb2 inhibit Ras activity via association with the yeast RasGAP neurofibromin homologs Ira1 and Ira2.

Publication ,  Journal Article
Harashima, T; Anderson, S; Yates, JR; Heitman, J
Published in: Mol Cell
June 23, 2006

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.

Duke Scholars

Published In

Mol Cell

DOI

ISSN

1097-2765

Publication Date

June 23, 2006

Volume

22

Issue

6

Start / End Page

819 / 830

Location

United States

Related Subject Headings

  • ras Proteins
  • Signal Transduction
  • Sequence Homology, Amino Acid
  • Saccharomyces cerevisiae Proteins
  • Saccharomyces cerevisiae
  • Repressor Proteins
  • Protein Structure, Tertiary
  • Protein Serine-Threonine Kinases
  • Protein Binding
  • Neurofibromin 1
 

Citation

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Harashima, T., Anderson, S., Yates, J. R., & Heitman, J. (2006). The kelch proteins Gpb1 and Gpb2 inhibit Ras activity via association with the yeast RasGAP neurofibromin homologs Ira1 and Ira2. Mol Cell, 22(6), 819–830. https://doi.org/10.1016/j.molcel.2006.05.011
Harashima, Toshiaki, Scott Anderson, John R. Yates, and Joseph Heitman. “The kelch proteins Gpb1 and Gpb2 inhibit Ras activity via association with the yeast RasGAP neurofibromin homologs Ira1 and Ira2.Mol Cell 22, no. 6 (June 23, 2006): 819–30. https://doi.org/10.1016/j.molcel.2006.05.011.
Harashima, Toshiaki, et al. “The kelch proteins Gpb1 and Gpb2 inhibit Ras activity via association with the yeast RasGAP neurofibromin homologs Ira1 and Ira2.Mol Cell, vol. 22, no. 6, June 2006, pp. 819–30. Pubmed, doi:10.1016/j.molcel.2006.05.011.
Journal cover image

Published In

Mol Cell

DOI

ISSN

1097-2765

Publication Date

June 23, 2006

Volume

22

Issue

6

Start / End Page

819 / 830

Location

United States

Related Subject Headings

  • ras Proteins
  • Signal Transduction
  • Sequence Homology, Amino Acid
  • Saccharomyces cerevisiae Proteins
  • Saccharomyces cerevisiae
  • Repressor Proteins
  • Protein Structure, Tertiary
  • Protein Serine-Threonine Kinases
  • Protein Binding
  • Neurofibromin 1