Role of the intracellular domains of CXCR4 in SDF-1-mediated signaling
| Autor: | Brendan J. Murphy, Keith E. Nye, Barbara Ahr, Vincent Delauzun, Joachim Roland, Martine Biard-Piechaczyk, Véronique Robert-Hebmann, Christian Devaux |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
MAPK/ERK pathway
Chemokine Cytoplasm Receptors CXCR4 media_common.quotation_subject Immunology Biology GTP-Binding Protein alpha Subunits Gi-Go Transfection Biochemistry Cell Line Chemokine receptor Humans Calcium Signaling Internalization media_common Cell chemotaxis Chemotaxis HEK 293 cells Cell Biology Hematology Chemokine CXCL12 Endocytosis Cell biology Protein Structure Tertiary Mutation biology.protein Signal transduction Mitogen-Activated Protein Kinases Chemokines CXC Signal Transduction |
| Zdroj: | Blood. 101(2) |
| ISSN: | 0006-4971 |
| Popis: | The CXCR4 chemokine receptor is a Gi protein–coupled receptor that triggers multiple intracellular signals in response to stromal cell-derived factor 1 (SDF-1), including calcium mobilization and p44/42 extracellular signal-regulated kinases (ERK1/2). Transduced signals lead to cell chemotaxis and are terminated through receptor internalization depending on phosphorylation of the C terminus part of CXCR4. Receptor endocytosis is also required for some receptors to stimulate ERK1/2 and to migrate through a chemokine gradient. In this study, we explored the role played by the 3 intracellular loops (ICL1-3) and the C terminus domain of CXCR4 in SDF-1–mediated signaling by using human embryonic kidney (HEK)–293 cells stably expressing wild-type or mutated forms of CXCR4. ICL3 of CXCR4 is specifically involved in Gi-dependent signals such as calcium mobilization and ERK activation, but does not trigger CXCR4 internalization after SDF-1 binding, indicating that ERK phosphorylation is independent of CXCR4 endocytosis. Surprisingly, ICL2, with or without the aspartic acid, arginine, and tyrosine (DRY) motif, is dispensable for Gi signaling. However, ICL2 and ICL3, as well as the C terminus part of CXCR4, are needed to transduce SDF-1–mediated chemotaxis, suggesting that this event involves multiple activation pathways and/or cooperation of several cytoplasmic domains of CXCR4. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|