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RGS4 inhibits platelet-activating factor receptor phosphorylation and cellular responses.

Publication ,  Journal Article
Richardson, RM; Marjoram, RJ; Barr, AJ; Snyderman, R
Published in: Biochemistry
March 27, 2001

To define the role of regulators of G-protein signaling (RGS) in chemoattractant-mediated responses, RGS4 and the receptors for platelet-activating factor (PAFR), formylated peptides (FR), or interleukin-8 (CXCR1) were stably coexpressed in a rat basophilic leukemia (RBL-2H3) cell line. The data demonstrate that RGS4 inhibited responses by PAFR (i.e., phosphoinositide (PI) hydrolysis, Ca2+ mobilization) but not by FR or CXCR1. An N-terminal 33 amino acid deletion mutant of RGS4 (DeltaRGS4), deficient in GAP (GTPase activating protein) activity and plasma membrane localization, had no effect on either PAFR, FR, or CXCR1. RGS4, but not DeltaRGS4, also blocked phosphorylation of PAFR by platelet-activating factor (PAF) and, unexpectedly, by phorbol 12-myristate 13-acetate (PMA); it also blocked cross-phosphorylation by formylmethionylleucylphenylalanine (fMLP). A point mutant of RGS4 (N88S), deficient in GAP activity but not membrane localization, partially blocked PAFR phosphorylation but had no effect on PAFR-mediated PI hydrolysis and Ca2+ mobilization. Truncation of the cytoplasmic tail of PAFR (mPAFR) resulted in a loss of its susceptibility to inhibition by RGS4. Taken together, the data indicate that of the receptors studied, RGS4 selectively inhibited responses to PAFR, which preferentially couples to Gq. At the level of expression studied, RGS4 did not inhibit FR or CXCR1 which activates Gi to transduce cellular signals. Since the tail-deleted mutant of PAFR was not affected by RGS4, and RGS4 blocked homologous as well as heterologous phosphorylation of this receptor, it is possible that RGS4 interferes sterically with the cytoplasmic tail of PAFR. Thus, in addition to stimulating the GTPase activity of Galpha, RGS4 prevents G protein activation by PAFR and the homologous and heterologous phosphorylation of this receptor.

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Published In

Biochemistry

DOI

ISSN

0006-2960

Publication Date

March 27, 2001

Volume

40

Issue

12

Start / End Page

3583 / 3588

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transfection
  • Receptors, Peptide
  • Receptors, Immunologic
  • Receptors, G-Protein-Coupled
  • Receptors, Formyl Peptide
  • Receptors, Cell Surface
  • Rats
  • RGS Proteins
  • Platelet Membrane Glycoproteins
 

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Richardson, R. M., Marjoram, R. J., Barr, A. J., & Snyderman, R. (2001). RGS4 inhibits platelet-activating factor receptor phosphorylation and cellular responses. Biochemistry, 40(12), 3583–3588. https://doi.org/10.1021/bi0019242
Richardson, R. M., R. J. Marjoram, A. J. Barr, and R. Snyderman. “RGS4 inhibits platelet-activating factor receptor phosphorylation and cellular responses.Biochemistry 40, no. 12 (March 27, 2001): 3583–88. https://doi.org/10.1021/bi0019242.
Richardson RM, Marjoram RJ, Barr AJ, Snyderman R. RGS4 inhibits platelet-activating factor receptor phosphorylation and cellular responses. Biochemistry. 2001 Mar 27;40(12):3583–8.
Richardson, R. M., et al. “RGS4 inhibits platelet-activating factor receptor phosphorylation and cellular responses.Biochemistry, vol. 40, no. 12, Mar. 2001, pp. 3583–88. Pubmed, doi:10.1021/bi0019242.
Richardson RM, Marjoram RJ, Barr AJ, Snyderman R. RGS4 inhibits platelet-activating factor receptor phosphorylation and cellular responses. Biochemistry. 2001 Mar 27;40(12):3583–3588.
Journal cover image

Published In

Biochemistry

DOI

ISSN

0006-2960

Publication Date

March 27, 2001

Volume

40

Issue

12

Start / End Page

3583 / 3588

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transfection
  • Receptors, Peptide
  • Receptors, Immunologic
  • Receptors, G-Protein-Coupled
  • Receptors, Formyl Peptide
  • Receptors, Cell Surface
  • Rats
  • RGS Proteins
  • Platelet Membrane Glycoproteins