The membrane proximal segment of the IL-2 receptor beta-chain acidic region is essential for IL2-dependent protein tyrosine kinase activation.
The signal transduction mechanism of the interleukin-2 receptor (IL-2R) remains largely undefined. The cytosolic domain of the IL-2R beta subunit is known to be essential for coupling to intracellular signaling pathways such as protein tyrosine kinase (PTK) and for control of IL-2 dependent cellular proliferation. A panel of cell lines that express IL-2R beta chains that contain sequential truncation mutations within the cytosolic domain were constructed. These cell lines were used to map the interaction of IL-2R with PTK activation, and the linkage of PTK function to activation of the enzyme phosphatidylinositol-3-kinase (Pl3K). The data show that the amino terminal segment of the acidic region (residues 314-350) within IL-2R beta is a critical site for PTK activation, and that activation of Pl3K is linked to IL-2 dependent tyrosine phosphorylation.
Williamson
P
P
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia 19104.
Merida
I
I
Greene
W C
WC
Gaulton
G
G
D000818:Animals; D002478:Cells, Cultured; D004789:Enzyme Activation; D007376:Interleukin-2 / Q000494:pharmacology*; D051379:Mice; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000502:physiology*
D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011505:Protein-Tyrosine Kinases