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.
Department of Medicine, University of California, San Francisco, California 94143-0711, USA.
Carola
C
Grinninger
Wengang
W
Wang
Kaveh Bastani
KB
Oskoui
Julia K
JK
Voice
Edward J
EJ
Goetzl
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