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Volume 272, Number 23, Issue of June 6, 1997 pp. 14586-14591
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Evidence for the Direct Involvement of Transmembrane Region 6 of the Lutropin/Choriogonadotropin Receptor in Activating G_s

(Received for publication, October 25, 1996, and in revised form, March 5, 1997)

From the Department of Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, Iowa 52242

The luteinizing hormone/chorionic gonadotropin receptor (LHR) is a heptahelical receptor that interacts primarily with G_s. Previous studies by others have shown that some forms of familial male precocious puberty are associated with mutations of the human LHR in the sixth transmembrane region that result in constitutive activation of the receptor. This study demonstrates that a peptide corresponding to the lower portion of the sixth transmembrane region of the LHR can significantly activate adenylyl cyclase activity. Experiments with membranes derived from wild-type versus cyc S49 cells demonstrate that the stimulation of cyclase by this peptide is due to an activation of G_s. As such, our data demonstrate a direct role for transmembrane region 6 of the rat LHR in activating G_s and therefore raise the possibility that mutations in transmembrane region 6 of the LHR may directly affect the coupling of the receptor to G_s. Significantly, these data are the first to demonstrate the ability of a transmembrane portion of a G protein-coupled receptor, in the absence of any contributions from an intracellular loop region, to activate a G protein.

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