Identification of the monomeric G-protein, Rhes, as an efaroxan-regulated protein in the pancreatic beta-cell.
Efaroxan induces membrane depolarization by interaction with the pore forming subunit of the ATP-sensitive potassium channel, Kir6.2. However, this effect is not responsible for its full secretory activity. In this study we have used an anti-idiotypic approach to generate antibodies that recognize additional proteins that may be regulated by efaroxan in pancreatic beta-cells. Using these antisera in an expression cloning strategy we have identified a monomeric GTP-binding protein, Rhes, as a potential target for regulation by imidazoline ligands. Rhes is shown to be expressed in beta-cells and its expression is regulated by efaroxan under conditions when a structurally related molecule, KU14R, is ineffective. The results reveal that beta-cells express Rhes and suggest that changes in the expression of this molecule may regulate the sensitivity of beta-cells to imidazoline secretagogues.
Chan
Sue L F
SL
Institute of Cell Signalling, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK.
Monks
Lara K
LK
Gao
Hongwei
H
Deaville
Pamela
P
Morgan
Noel G
NG
D000818:Animals; D000918:Antibody Specificity; D001572:Benzofurans / Q000276:immunology / Q000494:pharmacology*; D002478:Cells, Cultured; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D007093:Imidazoles / Q000276:immunology / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
D001572:Benzofurans; D007093:Imidazoles; D007328:Insulin; D019204:GTP-Binding Proteins; C442475:Rasd2 protein, rat; C062597:efaroxan