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J Biol Chem, Vol. 275, Issue 18, 13386-13393, May 5, 2000
From the Department of Pharmacology, University of Iowa College of
Medicine, Iowa City, Iowa 52242-1109
Using the C-terminal tail of the rat
lutropin/choriogonadotropin receptor (rLHR) as "bait" in a yeast
two-hybrid screen resulted in the identification of
p38JAB1 (a protein initially identified as a
co-activator of c-Jun) as a putative rLHR binding partner. More
recently p38JAB1 has been shown to promote the
degradation of a cyclin-dependent kinase inhibitor and to
be a component of the COP9 signalosome. Microscopic localization of an
epitope-tagged p38JAB1 expressed in 293 cells
revealed a punctuated perinuclear and cytosolic localization, while
cell fractionation studies showed that most of the
p38JAB1 was in a high speed supernatant.
Co-transfection of 293 cells revealed that
p38JAB1 binds to the immature 68-kDa precursor
of the rLHR that resides in the endoplasmic reticulum and promotes its
degradation. It does not appear to interact with the cell surface rLHR,
however, and it does not affect its expression. When transfected into
HeLa cells, p38JAB1 potentiates the
transcriptional activity of c-Jun, but co-transfection with rLHR
prevents this effect. We conclude that p38JAB1
interacts with the rLHR precursor and promotes its degradation. These
results reveal a novel protein binding partner of the rLHR and are
consistent with current views of the functions of
p38JAB1.
p38JAB1 Binds to the Intracellular
Precursor of the Lutropin/Choriogonadotropin Receptor and Promotes Its
Degradation*
*
This work was supported by National Institutes of Health
Grant CA-40629 (to M. A.). The services and facilities provided by the Diabetes and Endocrinology Research Center of the University of
Iowa were supported by National Institutes of Health Grant DK-25295.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,
2-319A BSB, 51 Newton Rd., University of Iowa, Iowa City, IA
52242-1109. Tel.: 319-335-9907; Fax: 319-335-8930; E-mail: mario-ascoli@uiowa.edu.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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