Trans-activation, cis-activation and signal selection of gonadotropin receptors.
It has been thought that when a hormone binds to a receptor, the liganded receptor activates itself and generates hormone signals, such as the cAMP signal and the inositol phosphate signal (cis-activation). We describe that a liganded LH receptor or FSH receptor molecule is capable of intermolecularly activating nonliganded receptors (trans-activation). Particularly, intriguing is the possibility that a pair of compound heterozygous mutants, one defective in binding and the other defective in signaling, may cooperate and rescue signaling. Furthermore, trans-activation of the binding deficient receptors examined in our studies generates either the cAMP signal or the IP signal, but not both. Trans-activation and selective signal generation have broad implications on signal generation mechanisms, and suggest new therapeutic approaches.
Jeoung
MyoungKun
M
Department of Chemistry, University of Kentucky, Lexington, KY 40506-0055, United States.
Lee
ChangWoo
C
Ji
Inhae
I
Ji
Tae H
TH
D000595:Amino Acid Sequence; D000242:Cyclic AMP / Q000096:biosynthesis; D006062:Gonadotropins / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D000090263:Leucine-Rich Repeat Proteins; D008957:Models, Genetic; D008969:Molecular Sequence Data; D019920:Photoaffinity Labels; D017434:Protein Structure, Tertiary / Q000187:drug effects; D011506:Proteins / Q000737:chemistry; D011962:Receptors, FSH / Q000235:genetics* / Q000378:metabolism*; D011974:Receptors, LH / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects
D006062:Gonadotropins; D000090263:Leucine-Rich Repeat Proteins; D019920:Photoaffinity Labels; D011506:Proteins; D011962:Receptors, FSH; D011974:Receptors, LH; D000242:Cyclic AMP