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Phenotypic changes induced by interleukin 2 il 2 and il 3 in an immature t lymphocytic leukemia are associated with regulated expression of il 2 receptor beta chain and of protein tyrosine kinases lck and lyn

Phenotypic changes induced by interleukin 2 il 2 and il 3 in an immature t lymphocytic leukemia are associated with regulated expression of il 2 receptor beta chain and of protein tyrosine kinases lck and lyn

Blood 80(4): 1017-1025

We have previously reported the establishment of an interleukin-3 (IL-3)-dependent and phenotypically myeloid cell line (TALL-103/3), obtained by culturing cells from an immature T-lymphoblastic leukemia in the presence of IL-3. These cells differentiated into a T-lymphoid cell line (TALL-103/2) upon removal of IL-3 and incubation in IL-2. Despite the different phenotype, the two cells lines remained karyotypically and genotypically identical. Here, we have analyzed the phenotypic changes and the signaling event induced by these two lymphokines in TALL-103/3 cells by switching them to temporary growth in IL-2 and returning them to IL-3. All four sublines obtained (the myeloid in IL-3 and the lymphoid in IL-2) expressed RNA for CD3, IL-2 receptor (R) .alpha., and T-cell receptor(TCR)-.gamma. and -.delta. chains. However, cells cultured in IL-3 failed to express detectable levels of the IL-2R .beta. chain at both the protein and RNA levels, whereas cells exposed to IL-2 always expressed IL-2R .beta. In parallel with the changes in IL-2R .beta. expression, the SRC-like protein tyrosine kinase (PTK) p56 LCK could not be detected in IL-3-dependent cells, but was abundant in the IL-2-dependent cells and underwent markedly increased autophosphorylation in response to IL-2. In contrast, p53/p56 LYN was highly expressed in IL-3-dependent cells, and greatly decreased when these cells were switched to growth in IL-2. LYN kinase autophosphorylation modestly increased in response to IL-3. None of the other kinases in the SRC family that were tested underwent increased autophosphorylation after lymphokine stimulation, indicating the specificity of IL-2 for LCK and of IL-3 for LYN. The TALL-103 cell lines provide a unique system to study the interaction between lymphokines and SRC-family PTKs in signal transduction pathways leading to hematopoietic cell differentiation.

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Accession: 007649698

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PMID: 1379847

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