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PMID: 9144190 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Molecular uncoupling of C-C chemokine receptor 5-induced chemotaxis and signal transduction from HIV-1 coreceptor activity.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 94 ·No. 10 ·1997-05-13 ·Pages 5061-6

Gosling J, Monteclaro FS, Atchison RE, Arai H, Tsou CL, Goldsmith MA, Charo IF

Abstract

The C-C chemokine receptor 5 (CCR5) plays a crucial role in facilitating the entry of macrophage-tropic strains of the HIV-1 into cells, but the mechanism of this phenomenon is completely unknown. To explore the role of CCR5-derived signal transduction in viral entry, we introduced mutations into two cytoplasmic domains of CCR5 involved in receptor-mediated function. Truncation of the terminal carboxyl-tail to eight amino acids or mutation of the highly conserved aspartate-arginine-tyrosine, or DRY, sequence in the second cytoplasmic loop of CCR5 effectively blocked chemokine-dependent activation of classic second messengers, intracellular calcium fluxes, and the cellular response of chemotaxis. In contrast, none of the mutations altered the ability of CCR5 to act as an HIV-1 coreceptor. We conclude that the initiation of signal transduction, the prototypic function of G protein coupled receptors, is not required for CCR5 to act as a coreceptor for HIV-1 entry into cells.

MeSH Terms
Amino Acid Sequence Binding Sites Calcium Cell Line Chemokine CCL4 Chemokine CCL5/metabolism,pharmacology Chemotaxis/drug effects,physiology Cloning, Molecular HIV-1/physiology Humans Kidney Kinetics Macrophage Inflammatory Proteins/metabolism,pharmacology Models, Structural Molecular Sequence Data Mutagenesis, Site-Directed Protein Structure, Secondary Receptors, CCR5 Receptors, Cytokine/biosynthesis,chemistry,physiology Receptors, HIV/biosynthesis,chemistry,physiology Recombinant Proteins/chemistry,metabolism,pharmacology Second Messenger Systems Sequence Deletion Signal Transduction
Chemicals
Chemokine CCL4 Chemokine CCL5 Macrophage Inflammatory Proteins Receptors, CCR5 Receptors, Cytokine Receptors, HIV Recombinant Proteins Calcium
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Gosling J
Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA 94110, USA.
Monteclaro F S
Atchison R E
Arai H
Tsou C L
Goldsmith M A
Charo I F
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.94.10.5061
Published
1997-05-13
Pages
5061-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC24631
Subset
IM
Grants
NHLBI NIH HHS · R01 HL052773 · United States
NHLBI NIH HHS · HL52773 · United States
External Links
PubMed source DOI: 10.1073/pnas.94.10.5061 PMC Full Text View journal details
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