Ligation of the T cell co-stimulatory receptor CD28 activates the serine-threonine protein kinase protein kinase B

Eur J Immunol. 1997 Oct;27(10):2495-501. doi: 10.1002/eji.1830271006.

Abstract

The intracellular signaling pathways activated upon ligation of the co-stimulatory receptor CD28 remain relatively ill-defined, although CD28 ligation does result in the strong association with, and activation of, phosphatidylinositol (PI) 3-kinase. The downstream effector targets of the CD28-activated PI 3-kinase-dependent signaling pathway remain poorly defined, but recent evidence from other systems has shown that Akt/protein kinase B (PKB) is a major target of PI 3-kinase and have indicated that a major function of PKB is the regulation of cell survival events. Given the strong coupling of CD28 to PI 3-kinase and the known protective effects of both CD28 and PI 3-kinase against apoptosis in different cell models, we investigated the effects of CD28 on PKB activation. We demonstrate that ligation of CD28 by either anti-CD28 monoclonal antibodies or the natural ligand B7.1, results in the marked activation of PKB in both the leukemic T cell line Jurkat and freshly isolated human peripheral blood-derived normal T lymphocytes. Our data suggest therefore, that PKB may be an important intracellular signal involved in CD28 signal transduction and demonstrate CD28 coupling to downstream elements of a signaling cascade known to promote cell survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androstadienes / pharmacology
  • Antibodies, Monoclonal / pharmacology
  • B7-1 Antigen / immunology*
  • CD28 Antigens / immunology*
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Leukemia-Lymphoma, Adult T-Cell / pathology
  • Lymphocyte Activation / physiology*
  • Neoplasm Proteins / physiology
  • Phosphatidylinositol 3-Kinases / physiology
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein-Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / physiology*
  • Proto-Oncogene Proteins c-akt
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction / physiology*
  • T-Lymphocytes / immunology*
  • Tumor Cells, Cultured
  • Wortmannin

Substances

  • Androstadienes
  • Antibodies, Monoclonal
  • B7-1 Antigen
  • CD28 Antigens
  • Enzyme Inhibitors
  • Neoplasm Proteins
  • Phosphoinositide-3 Kinase Inhibitors
  • Proto-Oncogene Proteins
  • Recombinant Fusion Proteins
  • AKT1 protein, human
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Wortmannin