BCR ABL LEADS TO THE CONSTITUTIVE ACTIVATION OF STAT PROTEINS, AND SHARES AN EPITOPE WITH TYROSINE-PHOSPHORYLATED STATS/

Citation
Da. Frank et L. Varticovski, BCR ABL LEADS TO THE CONSTITUTIVE ACTIVATION OF STAT PROTEINS, AND SHARES AN EPITOPE WITH TYROSINE-PHOSPHORYLATED STATS/, Leukemia, 10(11), 1996, pp. 1724-1730
Citations number
36
Categorie Soggetti
Hematology,Oncology
Journal title
ISSN journal
08876924
Volume
10
Issue
11
Year of publication
1996
Pages
1724 - 1730
Database
ISI
SICI code
0887-6924(1996)10:11<1724:BALTTC>2.0.ZU;2-A
Abstract
The mechanism by which BCR/abl leads to the transformation of hematopo ietic cells is not understood. The introduction of BCR/abl into BaF3 c ells, an IL-3-dependent pro-lymphocytic cell line, abrogates the requi rement of IL-3 for growth, Given that IL-3 leads to the phosphorylatio n of Stat proteins, we tested the hypothesis that BCR/abl transformati on of hematopoietic cells induces the phosphorylation of Stats. We fou nd that BaF3 cells transformed by either the p190 or p210 forms of BCR /abl possess constitutively phosphorylated Stat1 and Stat5. Phosphoryl ation of Stat proteins was greater in cells transformed by p190 BCR/ab l than in cells transformed by p210 BCR/abl, suggesting that the magni tude of phosphorylation of Stat, proteins may play a role in the, biol ogical effects of BCR/abl. Expression of BCR/abl containing a mutation (Y177F) that prevents its interaction with GRB2 led to a decrease in the phosphorylation of Stat1 and Stat5. This suggested that GRB2, or i ts binding site on BCR/abl, may participate in the phosphorylation of Stat proteins. We also observed that the antiphospho-Stat antibody dir ectly recognized both the p190 and p210 forms of BCR/abl. This indicat ed that a tyrosine residue that becomes phosphorylated in BCR/abl may share homology with the tyrosine phosphorylation site of Stat1 and Sta t5. These findings may have implications for the mechanisms by which B CR/abl interacts with signaling pathways to confer growth factor indep endence and induce transformation of hematopoietic cells.