Targeted knock-in mice expressing mutations of CD28 reveal an essential pathway for costimulation.

ABSTRACT: Despite extensive study, the role of phosphatidylinositol 3-kinase (PI3-kinase) activation in CD28 function has been highly contentious. To definitively address this question, we generated knock-in mice expressing mutations in two critical domains of the cytoplasmic tail of CD28. Mutation of the proximal tyrosine motif interrupted PI3-kinase binding and prevented CD28-dependent phosphorylation of protein kinase B (PKB)/Akt; however, there was no detectable effect on interleukin-2 (IL-2) secretion, expression of Bcl-X(L), or on T-cell function in vivo. Furthermore, we demonstrate that signaling initiated by the C-terminal proline motif is directly responsible for tyrosine phosphorylation of phosphoinosotide-dependent kinase 1, protein kinase C theta, and glycogen synthase kinase 3beta, as w

SUBMITTER: Dodson LF 

PROVIDER: S-EPMC2698768 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature