Cocaine- and amphetamine-regulated transcript (CART) peptide activates the extracellular signal-regulated kinase (ERK) pathway in AtT20 cells via putative G-protein coupled receptors.
CART peptides are important neurotransmitters, but little is known about their receptors or signaling pathways in cells. In this study we describe the effects of CART 55-102 on the stimulation of extracellular signal-related kinase (ERK) in a pituitary-derived cell line. CART 55-102 treatment resulted in markedly enhanced ERK phosphorylation in AtT20 and GH3 cells, but had no significant effect on ERK phosphorylation levels in a variety of other cell types that were examined. The peptide activated ERK1 and 2 in AtT20 cells in a dose- and time-dependent manner, but an inactive peptide, CART 1-27, had no effect. U0126, an inhibitor of the MEK kinases, blocked the CART-stimulated activation of ERKs. ERK activation was also attenuated by pertussis toxin pre-treatment, but not by genistein, suggesting a Gi/o-dependent mechanism. Overall, these data strongly support the existence of a specific receptor for CART peptide that is a G-protein coupled receptor utilizing a Gi/o mechanism involving MEK1 and 2.
Lakatos
Anita
A
Yerkes National Primate Research Center of Emory University, 954 Gatewood Road, NE, Atlanta, GA 30329, USA.
Prinster
Steven
S
Vicentic
Aleksandra
A
Hall
Randy A
RA
Kuhar
Michael J
MJ
D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002070:Butadienes / Q000494:pharmacology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D019833:Genistein / Q000494:pharmacology; D051379:Mice; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009570:Nitriles / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D037342:Pertussis Toxin / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D010902:Pituitary Gland / Q000166:cytology; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
D002070:Butadienes; D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; D009570:Nitriles; D010446:Peptide Fragments; D043562:Receptors, G-Protein-Coupled; C113580:U 0126; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D019833:Genistein; D037342:Pertussis Toxin; D048049:Extracellular Signal-Regulated MAP Kinases