Engagement of interleukin-7 receptor stimulates tyrosine phosphorylation, phosphoinositide turnover, and clonal proliferation of human T-lineage acute lymphoblastic leukemia cells
| Autor: | Lisa Tuel-Ahlgren, Vedat Obuz, Kazimiera J. Gajl-Peczalska, Gary L. Schieven, Jeffrey A. Ledbetter, Ilker Dibirdik, Mridula Chandan Langlie, Kevin G. Waddick, Fatih M. Uckun |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
medicine.medical_specialty
medicine.drug_class Immunology Genistein Tyrosine phosphorylation Cell Biology Hematology Protein kinase inhibitor Biology Biochemistry Molecular biology chemistry.chemical_compound Endocrinology chemistry Cell surface receptor Internal medicine medicine Receptor Interleukin-7 receptor Protein kinase A Protein kinase C |
| Zdroj: | Blood. 78:564-570 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | The purposes of this study were to examine the biologic effects of the engagement of the interleukin-7 receptor (IL-7R) with recombinant human interleukin-7 (rhIL-7) in immunophenotypically distinct T-lineage acute lymphoblastic leukemia (ALL) blasts and to elucidate the biochemical nature of the IL-7R-linked transmembrane signal in rhIL-7-responsive T- lineage ALL blast populations. In the absence of costimulants, rhIL-7 stimulated the in vitro proliferation and colony formation of freshly isolated leukemic blasts from six to eight T-lineage ALL patients with a mean plating efficiency of 196 +/- 53 (background subtracted) colonies/10(5) blasts plated. Stimulation of T-lineage ALL blasts with rhIL-7 resulted in markedly enhanced tyrosine phosphorylation of six distinct phosphoproteins with molecular weights of 57, 72, 98, 123, 150, and 190 Kd, and induced a rapid increase in the production of inositol-1,4,5-trisphosphate (Ins-1,4,5-P3), which was inhibitable by the tyrosine-specific protein kinase inhibitor genistein, but not by the serine/threonine-specific protein kinase C inhibitor H7. Similarly, rhIL-7 stimulated Ins-1,4,5-P3 production in CEM-1.3 T-lineage ALL cells and this stimulation was inhibitable by the tyrosine-specific protein kinase inhibitors genistein and herbimycin A, but not by H-7. Thus, the transmembrane signal triggered by engagement of the IL-7R is intimately linked to a functional tyrosine-specific protein kinase pathway and stimulates the phosphoinositide (PI) turnover and proliferation of T-lineage ALL blasts. The presented data confirm and extend previous studies on the expression of functional IL-7R on T- lineage ALL blasts and support the hypothesis that IL-7 may play an important regulatory role in the biology of T-lineage ALL. |
| Databáze: | OpenAIRE |
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