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 phosphatidylinositol 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 p85 precipitates an 80-kDa tyrosine-phosphorylated protein (pp80) from the lysates of IL-2-stimulated, but not unstimulated, human T lymphoblasts. Preclearing studies and immunoblotting 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 corresponding to tyrosine 392 of the IL-2R beta chain partially inhibits binding of the IL-2R beta chain by p85 fusion protein, raising the possibility that this residue plays a role in the interaction of PI3-K with the receptor.
Truitt
K E
KE
Department of Medicine, University of California, San Francisco 94121.
Mills
G B
GB
Turck
C W
CW
Imboden
J B
JB
D000595:Amino Acid Sequence; D001665:Binding Sites; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D011233:Precipitin Tests; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000737:chemistry; D015375:Receptors, Interleukin-2 / Q000737:chemistry / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism
D009842:Oligopeptides; D010446:Peptide Fragments; D015375:Receptors, Interleukin-2; D014443:Tyrosine; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D017479:Receptors, Platelet-Derived Growth Factor; D016392:Proto-Oncogene Proteins pp60(c-src)