Selectivity in the Use of Gi/o Proteins Is Determined by the DRF Motif in CXCR6 and Is Cell-Type Specific

Molecular Pharmacology
Satya P SinghJoshua M Farber

Abstract

CXCR6, the receptor for CXCL16, is expressed on multiple cell types and can be a coreceptor for human immunodeficiency virus 1. Except for CXCR6, all human chemokine receptors contain the D(3.49)R(3.50)Y(3.51) sequence, and all but two contain A(3.53) at the cytoplasmic terminus of the third transmembrane helix (H3C), a region within class A G protein-coupled receptors that contacts G proteins. In CXCR6, H3C contains D(3.49)R(3.50)F(3.51)I(3.52)V(3.53) at positions 126-130. We investigated the importance and interdependence of the canonical D126 and the noncanonical F128 and V130 in CXCR6 by mutating D126 to Y, F128 to Y, and V130 to A singly and in combination. For comparison, we mutated the analogous positions D142, Y144, and A146 to Y, F, and V, respectively, in CCR6, a related receptor containing the canonical sequences. Mutants were analyzed in both human embryonic kidney 293T and Jurkat E6-1 cells. Our data show that for CXCR6 and/or CCR6, mutations in H3C can affect both receptor signaling and chemokine binding; noncanonical H3C sequences are functionally linked, with dual changes mitigating the effects of single mutations; mutations in H3C that compromise receptor activity show selective defects in the use of individual...Continue Reading

References

Jan 1, 1992·Annual Review of Pharmacology and Toxicology·J OstrowskiR J Lefkowitz
Nov 1, 1995·The Journal of Experimental Medicine·F LiaoJ M Farber
Sep 6, 1996·The Journal of Biological Chemistry·H Arai, I F Charo
Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
Dec 1, 1995·Proteins·D Frishman, P Argos
Feb 4, 1997·Proceedings of the National Academy of Sciences of the United States of America·A ScheerS Cotecchia
Mar 7, 1997·The Journal of Biological Chemistry·S AcharyaS S Karnik
Jul 17, 1997·Nature·G AlkhatibK W Peden
Mar 23, 2001·Nature Immunology·M MatloubianJ G Cyster
Feb 15, 2001·AIDS Research and Human Retroviruses·Y J ZhangJ P Moore
Mar 10, 2001·The Journal of Clinical Investigation·C H KimE C Butcher
Apr 6, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·A WilbanksM Briskin
Jun 9, 2001·Biochemical and Biophysical Research Communications·A ChenK A Jacobson
May 8, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Fang LiaoJoshua M Farber
Oct 24, 2002·Blood·Joachim RolandMartine Biard-Piechaczyk
May 20, 2004·The Journal of Biological Chemistry·Richard A ColvinAndrew D Luster
Sep 24, 2004·Cellular Signalling·Negin P MartinRobert J Lefkowitz
Jan 6, 2005·The Journal of Biological Chemistry·Yann PercherancierNikolaus Heveker
Jun 28, 2005·Cytokine & Growth Factor Reviews·Jean-Yves SpringaelMarc Parmentier
Oct 14, 2005·Journal of Computational Chemistry·James C PhillipsKlaus Schulten
Dec 29, 2006·Molecular Pharmacology·G Enrico RovatiRichard R Neubig
Apr 25, 2007·Proceedings of the National Academy of Sciences of the United States of America·Matthew R WhortonRoger K Sunahara
Jul 3, 2008·Nature·Tony WarneGebhard F X Schertler

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Citations

Mar 8, 2017·PloS One·Andrea KoenenDaniela Dreymueller
Nov 30, 2020·Cellular Signalling·Dylan Scott EigerSudarshan Rajagopal
Apr 4, 2021·International Journal of Molecular Sciences·Jan KorbeckiIrena Baranowska-Bosiacka
Oct 23, 2018·Trends in Pharmacological Sciences·Victoria A Blaho, Jerold Chun

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