II. Molecular characterization of GRP receptors. II.A. Most G protein-coupled receptors have an ARG in the 2nd intracellular loop and an ALA in the distal 3rd loop that are thought important in G-protein coupling. To investigate the cellular basis of GRP-R internalization, R139G and A263E GRP-R mutants were made. Neither activated phospholipase C (PLC), although both bound ligand with high affinities. Using these GRP-R mutants, GRP-R internalization was shown to be mediated by both PLC-dependent (50%) and independent (50%) processes and both required activation of G protein. II.B. Molecular characterization of receptors for CCK/gastric-related peptides. II.B.1. Chromosomal localization of CCK/A and CCK/B receptors in mouse and human. The gene encoding the CCK/A-R maps to a syntenic region of human chromosome 4 and mouse chromosome 5. The CCK/B-R is on a syntenic region of human chromosome 11 and distal mouse chromosome 7. II.B.2. Demonstration of 3 states of the CCK. Using the cloned CCK/A-R expressed in COS-7 cells and dispersed pancreatic acini, the CCKK/A-R was shown to exist in 3 affinity states rather than 2 states as previously widely-believed.
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| Ito, T; Igarashi, H; Pradhan, T K et al. (2001) GI side-effects of a possible therapeutic GRF analogue in monkeys are likely due to VIP receptor agonist activity. Peptides 22:1139-51 |
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