Signal transduction by the chemokine receptor CXCR5: Structural requirements for G protein activation analyzed by chimeric CXCR1/CXCR5 molecules

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Item Type:	Article
Title:	Signal transduction by the chemokine receptor CXCR5: Structural requirements for G protein activation analyzed by chimeric CXCR1/CXCR5 molecules
Creators Name:	Mueller, G. and Lipp, M.
Abstract:	The human chemokine receptors CXCR5 and CXCR1 activate signaling pathways via pertussis toxin-sensitive as well as insensitive G proteins. CXCR5 induces Ca2+ signaling and chemotaxis independently of inhibitory G proteins, whereas the same signaling pathways are entirely dependent on inhibitory G proteins for CXCR1. In contrast, activation of the MAP kinase cascade via ERK1/2 is a pertussis toxin-sensitive signaling event for both receptors. Using chimeric CXCR1/CXCR5 receptors we investigated structural requirements for the activation of signal transduction pathways by CXCR5. Individual or multiple intracellular domains of CXCR1 were exchanged for the corresponding sequences of CXCR5, leading to receptors resembling CXCR5 at the cytoplasmic surface to a varying extent. Replacing the second intracellular domain of CXCR1 had a major influence on signaling mediated by inhibitory G proteins, whereas the exchange of the third or carboxy-terminal intracellular domain had only minor effects on signal transduction. Activation of the MAP kinase cascade via ERK1/2 and chemotaxis are largely reduced in chimeras comprising the second intracellular domain of CXCR5, although coupling to inhibitory G proteins is retained in all chimeric receptors. In summary, these data characterize the contribution of the intracellular domains of CXCR5 to receptor signaling, thereby disclosing unique structural requirements that modulate G protein coupling by the receptor.
Keywords:	Chemokine, CXCL13, CXCL8, CXCR1, CXCR5
Source:	Biological Chemistry
ISSN:	1431-6730
Publisher:	de Gruyter
Volume:	382
Number:	9
Page Range:	1387-1397
Date:	1 January 2001
Official Publication:	https://doi.org/10.1515/BC.2001.171
PubMed:	View item in PubMed

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