Serine-Rich Region of the IL-2 Receptor β-Chain Is Required for Activation of Phosphatidylinositol 3-Kinase
Autor: | Takuya Kanazawa, Marilyn L. Keeler, Lyuba Varticovski |
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Rok vydání: | 1994 |
Předmět: |
Molecular Sequence Data
Immunology Gene Expression Phosphatidylinositol 3-Kinases Biology Cell Line chemistry.chemical_compound Serine Animals Humans Amino Acid Sequence Phosphatidylinositol IL-2 receptor Kinase activity Kinase Wild type Receptors Interleukin-2 Phosphoproteins Cell biology Enzyme Activation Phosphotransferases (Alcohol Group Acceptor) Biochemistry chemistry Mutation Interleukin-2 Tyrosine Signal transduction Tyrosine kinase Signal Transduction |
Zdroj: | Cellular Immunology. 156:378-388 |
ISSN: | 0008-8749 |
DOI: | 10.1006/cimm.1994.1183 |
Popis: | The intracellular portion of the IL-2 receptor (IL-2R) signal transducing beta-chain contains a distinct region, designated "serine-rich," which encompasses sequences required for IL-2-mediated cell growth. Although the receptor does not possess intrinsic protein-tyrosine kinase activity, IL-2 binding induces activation of intracellular protein-tyrosine kinases. Activation of many protein-tyrosine kinases leads to activation of phosphatidylinositol 3-kinase (PI 3-kinase). IL-2 binding also induces activation of PI 3-kinase. To study the interaction of PI 3-kinase with the IL-2 receptor beta-chain we analyzed PI 3-kinase activity in cells which express the wild type and mutant beta-chain. IL-2 mediated an increase in association with PI 3-kinase activity and protein in immunoprecipitates from cells expressing mitogenically competent receptors. PI 3-kinase products also increased in response to IL-2 in these cells. Deletion of the beta-chain serine-rich region abolished IL-2-mediated mitogenesis and cells expressing this mutant failed to activate PI 3-kinase. The interaction of the IL-2 receptor with an intracellular tyrosine kinase, lck, has been mapped to the acidic-rich region of the beta-chain. Cells which express the beta-chain lacking the acidic-rich region grow in the presence of IL-2 and had IL-2-dependent activation of PI 3-kinase. Activation of PI 3-kinase in response to IL-2 was not abolished by treatment of cells with rapamicin and occurred only in cells which express mitogenically competent receptors. The results presented in this study suggest that IL-2-mediated PI 3-kinase activation occurs by a mechanism distinct from interaction with the lck protein-tyrosine kinase. |
Databáze: | OpenAIRE |
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