| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Center for Basic Research in Digestive Diseases, Mayo Clinic and Foundation, Rochester, Minnesota 55905
The carboxy-terminal region of many guanine nucleotide-binding protein (G protein)-coupled receptors contains important regulatory sequences such as an NP(x)2-3Y motif, a site of fatty acid acylation, and serine- and threonine-rich domains. The type A CCK receptor contains all of these, yet their significance has not been examined. We have, therefore, constructed a series of receptor site mutants and truncations that interfere with each of these motifs and expressed each in Chinese hamster ovary cells where they were studied for radioligand binding, cell signaling, receptor internalization, and intracellular trafficking. Each construct was synthesized and transported appropriately to the cell surface, where CCK bound with high affinity, elicited an inositol 1,4,5-trisphosphate response, and resulted in internalization and normal trafficking. Thus modification or elimination of each of these established sequence motifs had no substantial effect on any of these parameters of receptor and cellular function. However, an additional construct that truncated the carboxy terminus, eliminating an additional 15-amino-acid segment devoid of any currently recognized sequence motifs, resulted in a marked change in receptor trafficking, with all other parameters of receptor function normal. This mutant receptor construct was delayed at the stage of early endosomes, delaying its progress to the lysosome-enriched perinuclear compartment from the rapid time course followed by wild-type receptor and all of the other constructs. It is proposed that this region of the CCK receptor tail contains a new motif important for intracellular receptor trafficking.
G protein-coupled receptor; receptor internalization; receptor trafficking; endocytosis; cholecystokinin
This article has been cited by other articles:
|
|
 |
|
  M. Dufresne, C. Seva, and D. Fourmy Cholecystokinin and gastrin receptors. Physiol Rev, July 1, 2006; 86(3): 805 - 847. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z.-J. Cheng and L. J. Miller Agonist-dependent Dissociation of Oligomeric Complexes of G Protein-coupled Cholecystokinin Receptors Demonstrated in Living Cells Using Bioluminescence Resonance Energy Transfer J. Biol. Chem., December 14, 2001; 276(51): 48040 - 48047. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Noble, S. A. Wank, J. N. Crawley, J. Bradwejn, K. B. Seroogy, M. Hamon, and B. P. Roques International Union of Pharmacology. XXI. Structure, Distribution, and Functions of Cholecystokinin Receptors Pharmacol. Rev., December 1, 1999; 51(4): 745 - 781. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Oliveira, A.C.M. Paiva, and G. Vriend A low resolution model for the interaction of G proteins with G protein-coupled receptors Protein Eng. Des. Sel., December 1, 1999; 12(12): 1087 - 1095. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. del Valle CCK receptor trafficking: a novel paradigm of travel. Focus on "Regulation of lateral mobility and cellular trafficking of the CCK receptor by a partial agonist" Am J Physiol Cell Physiol, March 1, 1999; 276(3): C537 - C538. [Full Text] [PDF]
|
|
|
|
|
|
E. M. Smyth, S. C. Austin, M. P. Reilly, and G. A. FitzGerald Internalization and Sequestration of the Human Prostacyclin Receptor J. Biol. Chem., October 6, 2000; 275(41): 32037 - 32045. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R.-M. Lyu, P. M. Germano, J. K. Choi, S. V. Le, and J. R. Pisegna Identification of an Essential Amino Acid Motif within the C Terminus of the Pituitary Adenylate Cyclase-activating Polypeptide Type I Receptor That Is Critical for Signal Transduction but Not for Receptor Internalization J. Biol. Chem., November 10, 2000; 275(46): 36134 - 36142. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
