Ganglioside (GM1) distinguishes the effects of CD4 on signal transduction through the TCR/CD3 complex in human lymphocytes

William J. Morrison, Kelly Young, Halina Offner, Arthur Vandenbark

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Ganglioside (GM1) modulation of CD4 off the surface of T lymphocytes defined functions of the CD4 molecule during signal transduction through the T cell receptor (TCR)/CD3 complex. Antibody cross-linking of CD3 alone (3 × 3) stimulated phospholiphase C (PLC) activity, rapid Ca2+ flux, and protein phosphorylations in freshly isolated human T lymphocytes. Antibody cross-linking of CD4 and CD3 (3 × 4) stimulated greater signaling than that caused by 3 × 3. Cross-linking CD4 alone did not stimulate these signaling processes. GM1-modulation of CD4 from the cell surface blocked all aspects of the augmented signaling imparted by CD4 co-modulation with CD3. In comparison, pretreatment with the protein tyrosine kinase inhibitor genistein inhibited 3 × 4-stimulated PLC activity and protein phosphorylation but not Ca2+ flux. Antibody cross-linking of the tyrosine phosphatase CD45 with 3 × 4 (3 × 4 × 45) also inhibited CD4-augmented phosphorylations and like genistein did not reduce Ca2+ levels. In conclusion, these data demonstrate that CD4 can augment signal transduction through the TCR/CD3 complex by its physical proximity to CD3. TCR/CD3-signaling augmentation by CD4 stimulated protein tyrosine kinases and PLC activities but stimulated intracellular Ca2+ flux through an independent mechanism(s).

Original languageEnglish (US)
Pages (from-to)159-165
Number of pages7
JournalCellular and Molecular Biology Research
Volume39
Issue number2
StatePublished - 1993

Fingerprint

CD3 Antigens
G(M1) Ganglioside
Signal transduction
Lymphocytes
T-Cell Antigen Receptor
Phosphorylation
Signal Transduction
Genistein
Protein-Tyrosine Kinases
T-cells
Antibodies
Modulation
Fluxes
T-Lymphocytes
CD4 Antigens
Protein Kinase Inhibitors
Protein C
Phosphoric Monoester Hydrolases
Tyrosine
Proteins

Keywords

  • CD4
  • Ganglioside
  • Signal transduction
  • T cell receptor

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this

@article{75360f1e32984021ae052d0217eef57f,
title = "Ganglioside (GM1) distinguishes the effects of CD4 on signal transduction through the TCR/CD3 complex in human lymphocytes",
abstract = "Ganglioside (GM1) modulation of CD4 off the surface of T lymphocytes defined functions of the CD4 molecule during signal transduction through the T cell receptor (TCR)/CD3 complex. Antibody cross-linking of CD3 alone (3 × 3) stimulated phospholiphase C (PLC) activity, rapid Ca2+ flux, and protein phosphorylations in freshly isolated human T lymphocytes. Antibody cross-linking of CD4 and CD3 (3 × 4) stimulated greater signaling than that caused by 3 × 3. Cross-linking CD4 alone did not stimulate these signaling processes. GM1-modulation of CD4 from the cell surface blocked all aspects of the augmented signaling imparted by CD4 co-modulation with CD3. In comparison, pretreatment with the protein tyrosine kinase inhibitor genistein inhibited 3 × 4-stimulated PLC activity and protein phosphorylation but not Ca2+ flux. Antibody cross-linking of the tyrosine phosphatase CD45 with 3 × 4 (3 × 4 × 45) also inhibited CD4-augmented phosphorylations and like genistein did not reduce Ca2+ levels. In conclusion, these data demonstrate that CD4 can augment signal transduction through the TCR/CD3 complex by its physical proximity to CD3. TCR/CD3-signaling augmentation by CD4 stimulated protein tyrosine kinases and PLC activities but stimulated intracellular Ca2+ flux through an independent mechanism(s).",
keywords = "CD4, Ganglioside, Signal transduction, T cell receptor",
author = "Morrison, {William J.} and Kelly Young and Halina Offner and Arthur Vandenbark",
year = "1993",
language = "English (US)",
volume = "39",
pages = "159--165",
journal = "Cellular and Molecular Biology Research",
issn = "0968-8773",
publisher = "Springer Verlag",
number = "2",

}

TY - JOUR

T1 - Ganglioside (GM1) distinguishes the effects of CD4 on signal transduction through the TCR/CD3 complex in human lymphocytes

AU - Morrison, William J.

AU - Young, Kelly

AU - Offner, Halina

AU - Vandenbark, Arthur

PY - 1993

Y1 - 1993

N2 - Ganglioside (GM1) modulation of CD4 off the surface of T lymphocytes defined functions of the CD4 molecule during signal transduction through the T cell receptor (TCR)/CD3 complex. Antibody cross-linking of CD3 alone (3 × 3) stimulated phospholiphase C (PLC) activity, rapid Ca2+ flux, and protein phosphorylations in freshly isolated human T lymphocytes. Antibody cross-linking of CD4 and CD3 (3 × 4) stimulated greater signaling than that caused by 3 × 3. Cross-linking CD4 alone did not stimulate these signaling processes. GM1-modulation of CD4 from the cell surface blocked all aspects of the augmented signaling imparted by CD4 co-modulation with CD3. In comparison, pretreatment with the protein tyrosine kinase inhibitor genistein inhibited 3 × 4-stimulated PLC activity and protein phosphorylation but not Ca2+ flux. Antibody cross-linking of the tyrosine phosphatase CD45 with 3 × 4 (3 × 4 × 45) also inhibited CD4-augmented phosphorylations and like genistein did not reduce Ca2+ levels. In conclusion, these data demonstrate that CD4 can augment signal transduction through the TCR/CD3 complex by its physical proximity to CD3. TCR/CD3-signaling augmentation by CD4 stimulated protein tyrosine kinases and PLC activities but stimulated intracellular Ca2+ flux through an independent mechanism(s).

AB - Ganglioside (GM1) modulation of CD4 off the surface of T lymphocytes defined functions of the CD4 molecule during signal transduction through the T cell receptor (TCR)/CD3 complex. Antibody cross-linking of CD3 alone (3 × 3) stimulated phospholiphase C (PLC) activity, rapid Ca2+ flux, and protein phosphorylations in freshly isolated human T lymphocytes. Antibody cross-linking of CD4 and CD3 (3 × 4) stimulated greater signaling than that caused by 3 × 3. Cross-linking CD4 alone did not stimulate these signaling processes. GM1-modulation of CD4 from the cell surface blocked all aspects of the augmented signaling imparted by CD4 co-modulation with CD3. In comparison, pretreatment with the protein tyrosine kinase inhibitor genistein inhibited 3 × 4-stimulated PLC activity and protein phosphorylation but not Ca2+ flux. Antibody cross-linking of the tyrosine phosphatase CD45 with 3 × 4 (3 × 4 × 45) also inhibited CD4-augmented phosphorylations and like genistein did not reduce Ca2+ levels. In conclusion, these data demonstrate that CD4 can augment signal transduction through the TCR/CD3 complex by its physical proximity to CD3. TCR/CD3-signaling augmentation by CD4 stimulated protein tyrosine kinases and PLC activities but stimulated intracellular Ca2+ flux through an independent mechanism(s).

KW - CD4

KW - Ganglioside

KW - Signal transduction

KW - T cell receptor

UR - http://www.scopus.com/inward/record.url?scp=0027168977&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027168977&partnerID=8YFLogxK

M3 - Article

C2 - 8106089

AN - SCOPUS:0027168977

VL - 39

SP - 159

EP - 165

JO - Cellular and Molecular Biology Research

JF - Cellular and Molecular Biology Research

SN - 0968-8773

IS - 2

ER -