Protein and lipid kinase activation cascades in interleukin-2 receptor signalling.
The signalling mechanisms of the IL-2R remained an enigma until recent years. We now know that IL-2R are coupled to their own unique signalling pathways that complement rather than duplicate TCR signalling. The IL-2R beta- and gamma-chains are essential for signal coupling. Sequence comparisons indicate that portions of the extracellular and cytoplasmic domains of IL2R beta gamma molecules are homologous to several hematopoietic growth factor receptors, including erythropoietin. This may indicate that these receptors utilize common or related molecules in ligand binding or signal transduction. The cytoplasmic domain of the IL-2R beta-chain contains distinctive serine (S) and acidic (A) rich regions that participate in signalling. The overall scheme of IL-2R signalling is similar to other eukaryotic growth factors in that ligand binding activates a complicated and branching series of enzymatic steps that utilize protein tyrosine kinase (PTK) activation as a central component. More recent reports indicate that IL-2R are linked to additional membrane and cytosolic signalling molecules, including glycosylated phosphatidylinositol (GPI), phosphatidylinositol-3-kinase (PI3K), p74c-raf and p21ras. The regulation of these factors and their importance in IL-2 induced growth and differentiation awaits further study.
Williamson
P
P
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia 19104.
Merida
I
I
Gaulton
G
G
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D019852:Diacylglycerol Kinase; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011519:Proto-Oncogenes; D015375:Receptors, Interleukin-2 / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction
D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D019852:Diacylglycerol Kinase; D011505:Protein-Tyrosine Kinases