Rv. Parry et al., LIGATION OF THE T-CELL COSTIMULATORY RECEPTOR CD28 ACTIVATES THE SERINE-THREONINE PROTEIN-KINASE PROTEIN-KINASE-B, European Journal of Immunology, 27(10), 1997, pp. 2495-2501
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 o
f, 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 i
ndicated that a major function of PKB is the regulation of cell surviv
al events. Given the strong coupling of CD28 to PI 3-kinase and the kn
own protective effects of both CD28 and PI 3-kinase against apoptosis
in different cell models, we investigated the effects of CD28 on PKB a
ctivation. We demonstrate that ligation of CD28 by either anti-CD28 mo
noclonal 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 survi
val.