Skip to main content

Role of phospholipase Cbeta3 phosphorylation in the desensitization of cellular responses to platelet-activating factor.

Publication ,  Journal Article
Ali, H; Fisher, I; Haribabu, B; Richardson, RM; Snyderman, R
Published in: J Biol Chem
May 2, 1997

Platelet-activating factor (PAF) stimulates a diverse array of cellular responses through receptors coupled to G proteins that activate phospholipase C (PLC). Truncation of the cytoplasmic tail of the receptor to remove phosphorylation sites (mutant PAF receptor, mPAFR) results in enhancement of PAF-stimulated responses. Here we demonstrate that PAF or phorbol 12-myristate 13-acetate (PMA) pretreatment inhibited wild type PAFR-induced PLC-mediated responses by approximately 90%, whereas these responses to the phosphorylation-deficient mPAFR were inhibited by approximately 50%, despite normal G protein coupling, suggesting a distal inhibitory locus. PAF and PMA, as well as a membrane permeable cyclic AMP analog, stimulated phosphorylation of PLCbeta3. A protein kinase C (PKC) inhibitor blocked phosphorylation of PLCbeta3 stimulated by PAF and PMA but not by cAMP. Activation of protein kinase A (PKA) by cAMP did not result in inhibition of Ca2+ mobilization stimulated by PAF. In contrast, cAMP did inhibit the response to formylpeptide chemoattractant receptor. These data suggest that homologous desensitization of PAF-mediated responses is regulated via phosphorylation at two levels in the signaling pathway, one at the receptor and the other at PLCbeta3 mediated by PKC but not by PKA. Phosphorylation of PLCbeta3 by PKA could explain the inhibition of formylpeptide chemoattractant receptor signaling by cAMP. As PAF and formylpeptide chemoattractant receptors activate PLC via different G proteins, phosphorylation of PLCbeta3 by PKC and PKA could provide distinct regulatory control for classes of G protein-coupled receptors.

Duke Scholars

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

May 2, 1997

Volume

272

Issue

18

Start / End Page

11706 / 11709

Location

United States

Related Subject Headings

  • Virulence Factors, Bordetella
  • Type C Phospholipases
  • Transfection
  • Thionucleotides
  • Tetradecanoylphorbol Acetate
  • Recombinant Proteins
  • Receptors, G-Protein-Coupled
  • Receptors, Cell Surface
  • Protein-Tyrosine Kinases
  • Platelet Membrane Glycoproteins
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Ali, H., Fisher, I., Haribabu, B., Richardson, R. M., & Snyderman, R. (1997). Role of phospholipase Cbeta3 phosphorylation in the desensitization of cellular responses to platelet-activating factor. J Biol Chem, 272(18), 11706–11709. https://doi.org/10.1074/jbc.272.18.11706
Ali, H., I. Fisher, B. Haribabu, R. M. Richardson, and R. Snyderman. “Role of phospholipase Cbeta3 phosphorylation in the desensitization of cellular responses to platelet-activating factor.J Biol Chem 272, no. 18 (May 2, 1997): 11706–9. https://doi.org/10.1074/jbc.272.18.11706.
Ali H, Fisher I, Haribabu B, Richardson RM, Snyderman R. Role of phospholipase Cbeta3 phosphorylation in the desensitization of cellular responses to platelet-activating factor. J Biol Chem. 1997 May 2;272(18):11706–9.
Ali, H., et al. “Role of phospholipase Cbeta3 phosphorylation in the desensitization of cellular responses to platelet-activating factor.J Biol Chem, vol. 272, no. 18, May 1997, pp. 11706–09. Pubmed, doi:10.1074/jbc.272.18.11706.
Ali H, Fisher I, Haribabu B, Richardson RM, Snyderman R. Role of phospholipase Cbeta3 phosphorylation in the desensitization of cellular responses to platelet-activating factor. J Biol Chem. 1997 May 2;272(18):11706–11709.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

May 2, 1997

Volume

272

Issue

18

Start / End Page

11706 / 11709

Location

United States

Related Subject Headings

  • Virulence Factors, Bordetella
  • Type C Phospholipases
  • Transfection
  • Thionucleotides
  • Tetradecanoylphorbol Acetate
  • Recombinant Proteins
  • Receptors, G-Protein-Coupled
  • Receptors, Cell Surface
  • Protein-Tyrosine Kinases
  • Platelet Membrane Glycoproteins