Trans-activation of mutant follicle-stimulating hormone receptors selectively generates only one of two hormone signals.
Previously, we reported that a liganded LH receptor (LHR) is capable of activating itself (cis-activation) and other nonliganded LHRs to induce cAMP (trans-activation). Trans-activation of the LHR raises two crucial questions. Is trans-activation unique to LHR or common to other G protein-coupled receptors? Does trans-activation stimulate phospholipase Cbeta as it does adenylyl cyclase? To address these questions, two types of novel FSH receptors (FSHRs) were constructed, one defective in hormone binding and the other defective in signal generation. The FSHR, a G protein-coupled receptor, comprises two major domains, the N-terminal extracellular exodomain that binds the hormone and the membrane-associated endodomain that generates the hormone signals. For signal defective receptors, the exodomain was attached to glycosyl phosphatidylinositol (ExoGPI) or the transmembrane domain of CD8 immune receptor (ExoCD). ExoGPI and ExoCD can trans-activate another nonliganded FSH. Surprisingly, the trans-activation generates a signal to activate either adenylyl cyclase or phospholipase Cbeta, but not both. These results indicate that trans-activation in these mutant receptors is selective and limited in signal generation, thus providing new approaches to investigating the generation of different hormone signals and a novel means to selectively generate a particular hormone signal. Our data also suggest that the FSHR's exodomain could not trans-activate LHR.
Ji
Inhae
I
Department of Chemistry, University of Kentucky, Lexington, KY 40506-0055, USA.
Lee
ChangWoo
C
Jeoung
MyoungKun
M
Koo
YongBum
Y
Sievert
Gail A
GA
Ji
Tae H
TH
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D018014:Gene Transfer Techniques; D006801:Humans; D007457:Iodine Radioisotopes / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism*; D009154:Mutation; D054799:Phospholipase C beta; D011962:Receptors, FSH / Q000235:genetics / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism*
D007457:Iodine Radioisotopes; D007527:Isoenzymes; D011962:Receptors, FSH; D000242:Cyclic AMP; D010738:Type C Phospholipases; D054799:Phospholipase C beta; D000262:Adenylyl Cyclases