SH2-DEPENDENT ASSOCIATION OF PHOSPHATIDYLINOSITOL 3'-KINASE 85-KDA REGULATORY SUBUNIT WITH THE INTERLEUKIN-2 RECEPTOR-BETA CHAIN

Interleukin-2 (IL-2) signaling results in tyrosine phosphorylation of the 75-kDa IL-2 receptor (IL-2R) beta chain and the activation of phos phatidylinositol 3'-kinase (PI3-K). Herein, we demonstrate that the 85 -kDa (p85) regulatory subunit of PI3-K physically associates with the tyrosine-phosphorylated IL-2R beta chain. A fusion protein containing both the amino- and the carboxyl-terminal src homology 2 domains of p8 5 precipitates an 80-kDa tyrosine-phosphorylated protein (pp80) from t he lysates of IL-2-stimulated, but not unstimulated, human T lymphobla sts. Preclearing studies and immunoblot ting with an antiserum to the IL-2R beta chain demonstrates that pp80 represents a portion of the IL -2R beta chain pool. A tyrosine-phosphorylated oligopeptide correspond ing to tyrosine 392 of the IL-2R beta chain partially inhibits binding of the IL-2R beta chain by p85 fusion protein, raising the possibilit y that this residue plays a role in the interaction of PI3-K with the receptor.