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J. Biol. Chem., Vol. 276, Issue 11, 7968-7973, March 16, 2001
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From the Department of Pharmacology, University of Iowa College of
Medicine, Iowa City, Iowa 52242-1109
Alanine scanning mutagenesis of the second
extracellular loop of the human lutropin receptor (hLHR) showed that
mutation of most of the residues present in this region either enhance
or impair the internalization of agonist. A more complete
analysis of four mutants, two that enhanced internalization (F515A and T521A) and two that impaired internalization (S512A and V519A), showed
that the two mutants that impaired internalization also show a decrease
in the sensitivity for agonist-induced cAMP accumulation, whereas the
two mutants that enhanced internalization show an increase in the
sensitivity for agonist-induced cAMP accumulation. None of these
mutants had an effect on the agonist-induced phosphorylation of the
hLHR, however. We conclude that, in contrast to the prevailing view of
the relative importance of receptor phosphorylation in the
internalization of G protein-coupled receptors, the phosphorylation of
the hLHR is less important than the agonist-induced activation of the
hLHR in the process of internalization.
Mutations of the Second Extracellular Loop of the Human Lutropin
Receptor Emphasize the Importance of Receptor Activation and
De-emphasize the Importance of Receptor Phosphorylation in
Agonist-induced Internalization*
*
This work was supported by National Institutes of Health
Grant CA-40629 (to M. A.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of Pharmacology,
University of Iowa, 2-319B BSB, 51 Newton Rd., Iowa City, IA
52242-1109. Tel.: 319-335-9907; Fax: 319-335-8930; E-mail: mario-ascoli@uiowa.edu.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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