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Localization of the RhoGEF Effector Activating Surface of Gα 13 to its Carboxy Terminus
Author(s) -
Hajicek Nicole,
Kreutz Barry,
Yau Douglas,
Nakamura Susumu,
Kozasa Tohru
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a257
Subject(s) - heterotrimeric g protein , g protein , guanine nucleotide exchange factor , gtpase , microbiology and biotechnology , gtp binding protein regulators , gtpase activating protein , fusion protein , gs alpha subunit , chimera (genetics) , biology , g protein coupled receptor , effector , gtp' , gq alpha subunit , signal transduction , chemistry , gene , genetics , biochemistry , recombinant dna , enzyme
The monomeric GTPase Rho regulates a variety of cellular processes, such as actin cytoskeletal rearrangement and gene expression. Two members of the heterotrimeric GTP‐binding protein (G‐protein) family, Gα 12 and Gα 13 , have been shown to mediate signals from G‐protein coupled receptors leading to Rho activation. In this novel signaling pathway, one of the guanine nucleotide exchange factors (GEFs) for Rho, p115RhoGEF, serves as a direct link between Gα 13 and Rho. The goal of the present study is to isolate the region of Gα 13 responsible for stimulating p115’s RhoGEF activity. To do this, three sets of Gα 12/13 and Gα 13/12 chimeras were constructed, in which the fusion point between Gα 12 and Gα 13 (or Gα 13 and Gα 12 ) was moved progressively towards the C‐terminus of the chimera. The resulting constructs represent chimeras with fusion points before and after the switch regions of Gα 12 and Gα 13 , as well as in the α4 helix. The results of in vitro experiments suggest that the region of Gα 13 responsible for stimulation of RhoGEF activity is localized to the C‐terminus of the switch regions. A precise delineation of the signaling pathway involving Gα 12 and Gα 13 , p115, and Rho will allow for a more complete understanding of the biochemical mechanism and physiological significance of Rho activation through G‐proteins. sources of support: National Institutes of Health (grant Gm 61454) and National Institutes of Health Pharmacological Sciences Training Program (grant Gm 070388)