Skip to main content

Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation.

Publication ,  Journal Article
Richardson, RM; Marjoram, RJ; Barak, LS; Snyderman, R
Published in: J Immunol
March 15, 2003

IL-8 (or CXCL8) activates the receptors CXCR1 (IL-8RA) and CXCR2 (IL-8RB) to induce chemotaxis in leukocytes, but only CXCR1 mediates cytotoxic and cross-regulatory signals. This may be due to the rapid internalization of CXCR2. To investigate the roles of the intracellular domains in receptor regulation, wild-type, chimeric, phosphorylation-deficient, and cytoplasmic tail (C-tail) deletion mutants of both receptors were expressed in RBL-2H3 cells and studied for cellular activation, receptor phosphorylation, desensitization, and internalization. All but one chimeric receptor bound IL-8 and mediated signal transduction, chemotaxis, and exocytosis. Upon IL-8 activation, the chimeric receptors underwent receptor phosphorylation and desensitization. One was resistant to internalization, yet it mediated normal levels of beta-arrestin 2 (beta arr-2) translocation. The lack of internalization by this receptor may be due to its reduced association with beta arr-2 and the adaptor protein-2 beta. The C-tail-deleted and phosphorylation-deficient receptors were resistant to receptor phosphorylation, desensitization, arrestin translocation, and internalization. They also mediated greater phosphoinositide hydrolysis and exocytosis and sustained Ca(2+) mobilization, but diminished chemotaxis. These data indicate that phosphorylation of the C-tails of CXCR1 and CXCR2 are required for arrestin translocation and internalization, but are not sufficient to explain the rapid internalization of CXCR2 relative to CXCR1. The data also show that receptor internalization is not required for chemotaxis. The lack of receptor phosphorylation was correlated with greater signal transduction but diminished chemotaxis, indicating that second messenger production, not receptor internalization, negatively regulates chemotaxis.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

March 15, 2003

Volume

170

Issue

6

Start / End Page

2904 / 2911

Location

United States

Related Subject Headings

  • src-Family Kinases
  • beta-Arrestins
  • beta-Arrestin 2
  • Tumor Cells, Cultured
  • Transfection
  • Recombinant Fusion Proteins
  • Receptors, Interleukin-8B
  • Receptors, Interleukin-8A
  • Rats
  • Phosphorylation
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Richardson, R. M., Marjoram, R. J., Barak, L. S., & Snyderman, R. (2003). Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J Immunol, 170(6), 2904–2911. https://doi.org/10.4049/jimmunol.170.6.2904
Richardson, Ricardo M., Robin J. Marjoram, Larry S. Barak, and Ralph Snyderman. “Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation.J Immunol 170, no. 6 (March 15, 2003): 2904–11. https://doi.org/10.4049/jimmunol.170.6.2904.
Richardson RM, Marjoram RJ, Barak LS, Snyderman R. Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J Immunol. 2003 Mar 15;170(6):2904–11.
Richardson, Ricardo M., et al. “Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation.J Immunol, vol. 170, no. 6, Mar. 2003, pp. 2904–11. Pubmed, doi:10.4049/jimmunol.170.6.2904.
Richardson RM, Marjoram RJ, Barak LS, Snyderman R. Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J Immunol. 2003 Mar 15;170(6):2904–2911.

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

March 15, 2003

Volume

170

Issue

6

Start / End Page

2904 / 2911

Location

United States

Related Subject Headings

  • src-Family Kinases
  • beta-Arrestins
  • beta-Arrestin 2
  • Tumor Cells, Cultured
  • Transfection
  • Recombinant Fusion Proteins
  • Receptors, Interleukin-8B
  • Receptors, Interleukin-8A
  • Rats
  • Phosphorylation