Interleukin-3 and p210 BCR/ABL activate both unique and overlapping pathways of signal transduction in a factor-dependent myeloid cell line.

摘要: Abstract Chronic myelogenous leukemia (CML) is characterized by a specific chromosomal translocation occurring between the long arms of chromosomes 9 and 22 resulting in fusion product, p210 BCR/ABL, which has elevated tyrosine kinase activity. Expression BCR/ABL murine interleukin-3 (IL-3)--dependent cell lines typically converts these to factor-independence non-autocrine mechanism. The IL-3 receptor believed function part activating receptor-associated kinase, leading hypothesis that may induce myeloid cells constitutively phosphorylating some common signal-transducing proteins normally would be phosphorylated on residues response IL-3. subclones were constructed from an IL-3-dependent line, 32Dcl3, transfection plasmid containing full-length cDNA. Following transfection, became completely factor-independent within 3 weeks. We examined effects pattern phosphorylation cellular 32Dcl3 using one- two-dimensional antiphosphotyrosine immunoblotting. WEHI-3B conditioned media (WEHI-CM) was used as source introduction results increased levels more than 20 new proteins, while WEHI-CM induced transient 6 10 proteins. Using immunoblots examine phosphoproteins, four categories could identified: (1) are inducibly only, (2) only BCR/ABL+ cells, (3) both (4) presence BCR/ABL. have identified one category 4 p42 mitogen-activated protein (MAP) (ERK2). Overall, however, we found signal transduction pathways strikingly different, suggesting most immediate substrates receptor-activated different. Convergence signaling at MAP interest since activation this been linked mitogenesis many systems. Identification overlapping help explain growth-promoting oncogene.