Membrane-proximal region of the carboxyl terminus of the gonadotropin-releasing hormone receptor (GnRHR) confers differential signal transduction between mammalian and nonmammalian GnRHRs

Da Young Oh, Jung Ah Song, Jung Sun Moon, Mi Jin Moon, Jae Il Kim, Kyungjin Kim, Hyuk Bang Kwon, Jae Young Seong

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Recently, we demonstrated that the mammalian type-l GnRH receptor (GnRHR) has a high preference for the phospholipase C/protein kinase C (PLC/PKC)-linked signaling pathway, whereas non-mammalian bullfrog (bf) GnRHRs couple to both adenylate cyclase/protein kinase A (AC/PKA)- and PLC/PKC-linked signaling pathways. In the present study, using AC/PKA-specific reporter (cAMP-responsive element-luciferase) and PLC/ PKC-specific reporter (serum-responsive element-luciferase) systems, we attempted to identify the motif responsible for this difference. A deletion of the intracellular carboxyl-terminal tail (C tail) of bfGnRHR-1 remarkably decreased its ability to induce the AC/PKA-linked signaling pathway. Further dissection of the C tail indicated that an HFRK motif in the membrane-proximal sequence of bfGnRHR-1 C tail is a minimal requirement for the AC/PKA-linked signaling pathway as the addition of this motif to rat GnRHR or deletion of it from bfGnRHR-1 significantly affected the ability to induce the AC/PKA-linked signaling pathway. Deletion or addition of the HFRK motif, however, did not critically influence the PLC/PKC-linked signaling pathway. These results indicate that the HFRK motif in the membrane-proximal region confers the differential signal transduction pathways between mammalian and nonmammalian GnRHRs.

Original languageEnglish
Pages (from-to)722-731
Number of pages10
JournalMolecular Endocrinology
Volume19
Issue number3
DOIs
Publication statusPublished - 2005 Mar 1
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

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