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Submitted on April 30, 2002
Accepted on November 20, 2002
1 Department of Pharmacology, The University of Iowa, Iowa City, Iowa 52242-1109 and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, 77030
* To whom correspondence should be addressed. E-mail: mario-ascoli{at}uiowa.edu.
Although highly homologous in amino acid sequence, the agonist-receptor complexes formed by the human (h) and rat (r) lutropin receptors (LHR) follow different intracellular routes. The agonist-rLHR complex is routed mostly to a lysosomal degradation pathway whereas a substantial portion of the agonist-hLHR complex is routed to a recycling pathway. In a previous study (Kishi, M., et.al., Mol. Endocrinol. 15: 1624-1535, 2001) we showed that grafting a five residue sequence (GTALL) present in the C-terminal tail of the hLHR into the equivalent position of the rLHR redirects a substantial portion of the internalized agonist-rLHR complex to a recycling pathway.
Using a number of mutations of the GTALL motif we now show that only the first two residues (GT) of this motif are necessary and sufficient to induce recycling of the internalized agonist-rLHR complex. Phosphoamino acid analysis and mutations of the GT motif show that phosphorylation of the threonine residue is not necessary for recycling. Lastly, we show that addition of portions of the C-terminal tail of the hLHR that include the GT motif to the C terminal tails of the rat follitropin (rFSHR) or murine 
-opioid receptors (mDOR) promotes the post-endocytotic recycling of these G protein-coupled receptors (GPCRs).
We conclude that the GT motif present in the C-terminal tail of the hLHR is a transferable motif that promotes the post-endocytotic recycling of several GPCRs and that the GT-induced recycling does not require the phosphorylation of the threonine residue.
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