A natural variant type II G protein-coupled receptor for vasoactive intestinal peptide with altered function.
The vasoactive intestinal peptide (VIP) and its G protein-coupled receptors VPAC1 and VPAC2 prominently mediate diverse physiological functions in the neural, endocrine, and immune systems. A deletion variant of mouse VPAC2 has been identified in immune cells that lacks amino acids 367-380 at the carboxyl-terminal end of the seventh transmembrane domain. When expressed at equivalent levels in a human Jurkat T cell line, which has very low endogenous expression of human VPAC1 and VPAC2, wild-type and deletion-variant VPAC2 bound the same amount of 125I-VIP with similar affinity. Unlike wild-type VPAC2, however, deletion-variant VPAC2 did not transduce VIP-elicited increases in intracellular concentration of cyclic AMP, chemotaxis, or suppression of generation of interleukin-2. Natural deletion of part of the last transmembrane domain of VPAC2 thus abrogates signaling functions without apparent alterations of expression or ligand binding.
Grinninger
Carola
C
Department of Medicine, University of California, San Francisco, California 94143-0711, USA.
Wang
Wengang
W
Oskoui
Kaveh Bastani
KB
Voice
Julia K
JK
Goetzl
Edward J
EJ
D000818:Animals; D002633:Chemotaxis; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D019169:Jurkat Cells; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000378:metabolism; D018005:Receptors, Vasoactive Intestinal Peptide / Q000737:chemistry* / Q000378:metabolism; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D015398:Signal Transduction; D014162:Transfection; D014660:Vasoactive Intestinal Peptide / Q000737:chemistry* / Q000378:metabolism
D007376:Interleukin-2; D008024:Ligands; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D018005:Receptors, Vasoactive Intestinal Peptide; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; C495509:VIPR2 protein, human; C495510:Vipr2 protein, mouse; D014660:Vasoactive Intestinal Peptide; D000242:Cyclic AMP