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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Gripentrog, Jeannie M. Oppermann, Martin Miettinen, Heini M. Suvorova, Elena S. |
| Description | Author Affiliation: Suvorova ES ( Department of Microbiology, Montana State University, Bozeman, MT 59717, USA.) |
| Abstract | The carboxyl tail of G protein-coupled receptors contains motifs that regulate receptor interactions with intracellular partners. Activation of the human neutrophil complement fragment C5a receptor (C5aR) is terminated by phosphorylation of the carboxyl tail followed by receptor internalization. In this study, we demonstrated that bulky hydrophobic residues in the membrane-proximal region of the C5aR carboxyl tail play an important role in proper structure and function of the receptor: Substitution of leucine 319 with alanine (L319A) resulted in receptor retention in the endoplasmic reticulum, whereas a L318A substitution allowed receptor transport to the cell surface, but showed slow internalization upon activation, presumably due to a defect in phosphorylation by both PKC and GRK. Normal agonist-induced activation of ERK1/2 and intracellular calcium release suggested that the L318A mutation did not affect receptor signaling. Binding of GRK2 and PKCbetaII to intracellular loop 3 of C5aR in vitro indicated that mutagenesis of L318 did not affect kinase binding. Limited proteolysis with trypsin revealed a conformational difference between wild type and mutant receptor. Our studies support a model in which the L318/L319 stabilizes an amphipathic helix (Q305-R320) in the membrane-proximal region of C5aR. |
| ISSN | 00063002 |
| Journal | Biochimica et Biophysica Acta (BBA) - Reviews on Cancer |
| Issue Number | 6 |
| Volume Number | 1783 |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2008-06-01 |
| Publisher Place | Netherlands |
| Access Restriction | Open |
| Subject Keyword | Endocytosis Leucine Chemistry Receptors, Complement Metabolism Amino Acid Sequence Amino Acid Substitution Animals Blotting, Western CHO Cells Calcium Cell Membrane Cricetinae Cricetulus Endoplasmic Reticulum Fluorescent Antibody Technique, Indirect G-Protein-Coupled Receptor Kinase 2 Genetics Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Molecular Sequence Data Mutagenesis, Site-Directed Neutrophils Phosphorylation Protein Conformation Protein Kinase C Protein Kinase C Beta Radioligand Assay Receptor, Anaphylatoxin C5a Recombinant Proteins Isolation & Purification Sequence Homology, Amino Acid Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Biochemistry |
| Content Type | Text |
| Resource Type | Article |
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