Determinants at the N- and C-termini of Gα12 required for activation of Rho-mediated signaling
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Ritchie, Benjamin J, et al. Determinants At the N- and C-termini of Gα12 Required for Activation of Rho-mediated Signaling. BioMed Central Ltd, 2013. https://doi.org/10.17615/re5s-h883APA
Ritchie, B., Smolski, W., Montgomery, E., Fisher, E., Choi, T., Olson, C., Foster, L., & Meigs, T. (2013). Determinants at the N- and C-termini of Gα12 required for activation of Rho-mediated signaling. BioMed Central Ltd. https://doi.org/10.17615/re5s-h883Chicago
Ritchie, Benjamin J, William C Smolski, Ellyn R Montgomery, Elizabeth S Fisher, Tina Y Choi, Calla M Olson, Lori A Foster et al. 2013. Determinants At the N and C-Termini of Gα12 Required for Activation of Rho-Mediated Signaling. BioMed Central Ltd. https://doi.org/10.17615/re5s-h883- Creator
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Ritchie, Benjamin J
- Other Affiliation: Department of Biology, University of North Carolina at Asheville, One University Heights, Asheville, NC 28804, USA
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Smolski, William C
- Other Affiliation: Department of Biology, University of North Carolina at Asheville, One University Heights, Asheville, NC 28804, USA
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Montgomery, Ellyn R
- Other Affiliation: Department of Biology, University of North Carolina at Asheville, One University Heights, Asheville, NC 28804, USA
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Fisher, Elizabeth S
- Other Affiliation: Department of Biology, University of North Carolina at Asheville, One University Heights, Asheville, NC 28804, USA
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Choi, Tina Y
- Other Affiliation: Department of Biology, University of North Carolina at Asheville, One University Heights, Asheville, NC 28804, USA
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Olson, Calla M
- Other Affiliation: Department of Biology, University of North Carolina at Asheville, One University Heights, Asheville, NC 28804, USA
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Foster, Lori A
- Other Affiliation: Department of Biology, University of North Carolina at Asheville, One University Heights, Asheville, NC 28804, USA
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Meigs, Thomas E
- Other Affiliation: Department of Biology, University of North Carolina at Asheville, One University Heights, Asheville, NC 28804, USA
- Abstract
- Background Heterotrimeric guanine nucleotide binding proteins of the G12/13 subfamily, which includes the α-subunits Gα12 and Gα13, stimulate the monomeric G protein RhoA through interaction with a distinct subset of Rho-specific guanine nucleotide exchange factors (RhoGEFs). The structural features that mediate interaction between Gα13 and RhoGEFs have been examined in crystallographic studies of the purified complex, whereas a Gα12:RhoGEF complex has not been reported. Several signaling responses and effector interactions appear unique to Gα12 or Gα13, despite their similarity in amino acid sequence. Methods To comprehensively examine Gα12 for regions involved in RhoGEF interaction, we screened a panel of Gα12 cassette substitution mutants for binding to leukemia-associated RhoGEF (LARG) and for activation of serum response element mediated transcription. Results We identified several cassette substitutions that disrupt Gα12 binding to LARG and the related p115RhoGEF. These Gα12 mutants also were impaired in activating serum response element mediated signaling, a Rho-dependent response. Most of these mutants matched corresponding regions of Gα13 reported to contact p115RhoGEF, but unexpectedly, several RhoGEF-uncoupling mutations were found within the N- and C-terminal regions of Gα12. Trypsin protection assays revealed several mutants in these regions as retaining conformational activation. In addition, charge substitutions near the Gα12 N-terminus selectively disrupted binding to LARG but not p115RhoGEF. Conclusions Several structural aspects of the Gα12:RhoGEF interface differ from the reported Gα13:RhoGEF complex, particularly determinants within the C-terminal α5 helix and structurally uncharacterized N-terminus of Gα12. Furthermore, key residues at the Gα12 N-terminus may confer selectivity for LARG as a downstream effector.
- Date of publication
- March 25, 2013
- DOI
- Identifier
- Resource type
- Article
- Rights statement
- In Copyright
- Rights holder
- Benjamin J Ritchie et al.; licensee BioMed Central Ltd.
- License
- Journal title
- Journal of Molecular Signaling
- Journal volume
- 8
- Journal issue
- 1
- Page start
- 3
- Language
- English
- Is the article or chapter peer-reviewed?
- Yes
- ISSN
- 1750-2187
- Bibliographic citation
- Journal of Molecular Signaling. 2013 Mar 25;8(1):3
- Publisher
- BioMed Central Ltd
- Access right
- Open Access
- Date uploaded
- April 25, 2013
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