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Submitted on June 1, 2004
Accepted on November 17, 2004
Hormone Research Center (D.Y.O., J.A.S., J.S.M., M.J.M., H.B.K., J.Y.S.), School of Biological Sciences and Technology, Chonnam National University, Gwangju 500-757, Korea; School of Biological Sciences (K.K.), Seoul National University, Seoul 151-742, Korea; Department of Life Science (J.I.K.), Kwangju Institute of Science and Technology, Gwangju 500-712, Korea
* To whom correspondence should be addressed. E-mail: jyseong{at}jnu.ac.kr.
Recently, we demonstrated that the mammalian type-I GnRH receptor (GnRHR) has a high preference for the phospholipase C/protein kinase C (PLC/PKC)-linked signaling pathway, while nonmammalian bullfrog GnRHRs (bfGnRHRs) 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 (CRE-luc) and PLC/PKC-specific reporter (SRE-luc) 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.
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