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Cross-desensitization of chemoattractant receptors occurs at multiple levels. Evidence for a role for inhibition of phospholipase C activity.

Publication ,  Journal Article
Richardson, RM; Ali, H; Tomhave, ED; Haribabu, B; Snyderman, R
Published in: J Biol Chem
November 17, 1995

To define the molecular mechanisms of cross-regulation among chemoattractant receptors, we stably coexpressed, in a rat basophilic leukemia (RBL-2H3) cell line, epitope-tagged receptors for the chemoattractants formylmethionylleucylphenylalanine (fMLP), a peptide of the fifth component of the complement system (C5a), and interleukin-8 (IL-8). All the expressed receptors underwent homologous phosphorylation and desensitization upon agonist stimulation. When co-expressed, epitope-tagged C5a receptor (ET-C5aR) and epitope-tagged IL-8 receptor (ET-IL-8RA) were cross-phosphorylated by activation of the other. Activation of epitope-tagged fMLP receptor (ET-FR) also cross-phosphorylated ET-C5aR and ET-IL-8RA, but ET-FR was totally resistant to cross-phosphorylation. Similarly, C5a and IL-8 stimulation of [35S]guanosine 5'-3-O-(thio) triphosphate (GTP gamma S) binding and Ca2+ mobilization were cross-desensitized by each other and by fMLP. Stimulation of [35S]GTP gamma S binding by fMLP was also not cross-desensitized by C5a or IL-8, however, Ca2+ mobilization was, suggesting a site of inhibition distal to G protein activation. Consistent with this desensitization of Ca2+ mobilization, inositol 1,4,5-trisphosphate release in RBL-2H3 cells expressing both ET-C5aR and ET-FR revealed that fMLP and C5a cross-desensitized each other's ability to stimulate phosphoinositide hydrolysis. Taken together, these results indicate that receptor cross-phosphorylation correlates directly with desensitization at the level of G protein activation. The ET-FR was resistant to this process. Of note, cross-desensitization of ET-FR at the level of phosphoinositide hydrolysis and Ca2+ mobilization was demonstrated in the absence of receptor phosphorylation. This suggests a new form of chemoattractant cross-regulation at a site distal to receptor/G protein coupling, involving the activity of phospholipase C.

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Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

November 17, 1995

Volume

270

Issue

46

Start / End Page

27829 / 27833

Location

United States

Related Subject Headings

  • Type C Phospholipases
  • Tumor Cells, Cultured
  • Recombinant Proteins
  • Receptors, Peptide
  • Receptors, Interleukin-8A
  • Receptors, Interleukin
  • Receptors, Immunologic
  • Receptors, Formyl Peptide
  • Receptors, Complement
  • Receptor, Anaphylatoxin C5a
 

Citation

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Richardson, R. M., Ali, H., Tomhave, E. D., Haribabu, B., & Snyderman, R. (1995). Cross-desensitization of chemoattractant receptors occurs at multiple levels. Evidence for a role for inhibition of phospholipase C activity. J Biol Chem, 270(46), 27829–27833. https://doi.org/10.1074/jbc.270.46.27829
Richardson, R. M., H. Ali, E. D. Tomhave, B. Haribabu, and R. Snyderman. “Cross-desensitization of chemoattractant receptors occurs at multiple levels. Evidence for a role for inhibition of phospholipase C activity.J Biol Chem 270, no. 46 (November 17, 1995): 27829–33. https://doi.org/10.1074/jbc.270.46.27829.
Richardson RM, Ali H, Tomhave ED, Haribabu B, Snyderman R. Cross-desensitization of chemoattractant receptors occurs at multiple levels. Evidence for a role for inhibition of phospholipase C activity. J Biol Chem. 1995 Nov 17;270(46):27829–33.
Richardson, R. M., et al. “Cross-desensitization of chemoattractant receptors occurs at multiple levels. Evidence for a role for inhibition of phospholipase C activity.J Biol Chem, vol. 270, no. 46, Nov. 1995, pp. 27829–33. Pubmed, doi:10.1074/jbc.270.46.27829.
Richardson RM, Ali H, Tomhave ED, Haribabu B, Snyderman R. Cross-desensitization of chemoattractant receptors occurs at multiple levels. Evidence for a role for inhibition of phospholipase C activity. J Biol Chem. 1995 Nov 17;270(46):27829–27833.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

November 17, 1995

Volume

270

Issue

46

Start / End Page

27829 / 27833

Location

United States

Related Subject Headings

  • Type C Phospholipases
  • Tumor Cells, Cultured
  • Recombinant Proteins
  • Receptors, Peptide
  • Receptors, Interleukin-8A
  • Receptors, Interleukin
  • Receptors, Immunologic
  • Receptors, Formyl Peptide
  • Receptors, Complement
  • Receptor, Anaphylatoxin C5a