The serine-rich cytoplasmic domain of the interleukin-2 receptor beta chain is essential for interleukin-2-dependent tyrosine protein kinase and phosphatidylinositol-3-kinase activation.
The biological activity of interleukin-2 receptors (IL-2R) is dependent on the functional coupling of IL-2R beta molecules to intracellular enzymes such as protein tyrosine kinase. The serine-rich, S-domain within the cytosolic portion of IL-2R beta plays an essential role in transduction of the IL-2 proliferative signal. Cells bearing either wild type IL-2R beta (Baf alpha/beta) or deletions within the S-domain (Baf alpha/beta SD1) were used to evaluate the importance of the S-domain in linking ligand binding to protein tyrosine kinase induction. Multiparameter, side by side comparisons showed that only those cells that expressed wild type IL-2R beta responded to IL-2 by increased cellular proliferation, accumulation of the c-myc proto-oncogene, and activation of protein tyrosine kinase. Activation of protein tyrosine kinase was, in turn, linked to increased tyrosine phosphorylation and activation of phosphatidylinositol-3-kinase. These findings indicate that the S-domain of the IL-2R beta chain is an essential component in the signal transduction cascade that links IL-2 binding to tyrosine kinase and phosphatidylinositol-3-kinase activation.
Merida
I
I
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104.
Williamson
P
P
Kuziel
W A
WA
Greene
W C
WC
Gaulton
G N
GN
D019870:1-Phosphatidylinositol 4-Kinase; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D004277:DNA, Single-Stranded; D004789:Enzyme Activation; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D010770:Phosphotransferases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000737:chemistry / Q000378:metabolism*; D012694:Serine / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism
D004277:DNA, Single-Stranded; D007376:Interleukin-2; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D012694:Serine; D010770:Phosphotransferases; D019870:1-Phosphatidylinositol 4-Kinase; D011505:Protein-Tyrosine Kinases; D013936:Thymidine