The effects of pertussis toxin and cholera toxin on mitogen-induced interleukin-2 production: evidence for G protein involvement in signal transduction

Cell Immunol. 1988 May;113(2):235-50. doi: 10.1016/0008-8749(88)90023-8.


GTP-binding proteins, known as G proteins, play important roles in transducing signals generated by the binding of specific ligands to cell surface receptors. We examined the possibility that a G protein is involved in transducing the concanavalin A (Con A) signal for IL-2 production using a T-cell hybridoma, FS6-14.13, and the bacterial toxins, pertussis toxin (PTX) and cholera toxin (CTX). These toxins are known to interact with and modify the functions of G proteins. High concentrations of PTX (25-50 micrograms/ml) stimulated IL-2 production in the FS-6 cells in the absence of Con A, presumably due to the ability of its B subunit to crosslink membrane proteins. However, in the presence of Con A, PTX inhibited IL-2 production at concentrations ranging from 0.05 to 50 micrograms/ml. It is unlikely that this inhibition was due to a competitive interaction between Con A and PTX for binding sites at the cell surface, since high concentrations of PTX only minimally reduced Con A-FITC binding, evaluated by FACS analysis. In addition, concentrations of PTX which were not able to stimulate IL-2 production in the absence of Con A, retained their ability to inhibit IL-2 production in the presence of Con A. These data suggest the involvement of the PTX A subunit in this activity. In support of this possibility, PTX catalyzed ADP-ribosylation of a Mr = 41,000-Da protein in FS-6 membranes. This strongly suggests that a PTX substrate is involved in transducing the Con A signal for IL-2 production in FS-6 cells. CTX also inhibited Con A-induced IL-2 production, an effect mimicked by the addition of dibutyryl-cAMP. This suggests that a CTX substrate linked to the adenylyl cyclase-cAMP pathway is probably not involved in transducing the stimulatory Con A signal, but may play a role in downregulating T-cell activation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Diphosphate Ribose / metabolism
  • Adenylate Cyclase Toxin*
  • Bucladesine / pharmacology
  • Cell Line
  • Cholera Toxin / pharmacology*
  • Concanavalin A / pharmacology
  • Dose-Response Relationship, Drug
  • GTP-Binding Proteins / physiology*
  • In Vitro Techniques
  • Interleukin-2 / biosynthesis*
  • Lymphocyte Activation / drug effects
  • Membrane Proteins / metabolism
  • Methylmannosides / pharmacology
  • Pertussis Toxin*
  • Receptors, Concanavalin A / metabolism
  • T-Lymphocytes / physiology*
  • Virulence Factors, Bordetella / pharmacology*


  • Adenylate Cyclase Toxin
  • Interleukin-2
  • Membrane Proteins
  • Methylmannosides
  • Receptors, Concanavalin A
  • Virulence Factors, Bordetella
  • Concanavalin A
  • Adenosine Diphosphate Ribose
  • methylmannoside
  • Bucladesine
  • Cholera Toxin
  • Pertussis Toxin
  • GTP-Binding Proteins