Src-homology region 2 (SH2) domains, by binding to tyrosine- phosphorylated sequences, mediate specific protein-protein interactions important in diverse signal transduction pathways. Previous studies have shown that activated forms of the Abl tyrosine kinase, including P210BCR/ABL of human chronic myelogenous leukemia, require the SH2 domain for the transformation of fibroblasts. To determine whether SH2 is also required for Bcr/Abl to transform hematopoietic cells, we have studied two SH2 domain mutations in P210BCR/ABL: a point mutation in the conserved FLVRES motif (P210/R1033K), which interferes with phosphotyrosine-binding by SH2, and a complete deletion of SH2 (P210/delta SH2). Despite a negative effect on intrinsic Abl kinase activity, both P210 SH2 mutants were still able to transform the hematopoietic factor-dependent cell lines Ba/F3 and FDC-P1 to growth factor independence. Unexpectedly, both mutants showed greater transforming activity than wild-type P210 in a quantitative transformation assay, probably as a consequence of increased stability of the SH2 mutant proteins in vivo. Cells transformed by both P210 SH2 mutants were leukemogenic in synaptic mice and P210/r1053K mice exhibited a distinct disease phenotype, reminiscent of that induced by v-Abl. These results demonstrate that while the Abl SH2 domain is essential for BCR/ABL transformation of fibroblasts, it is dispensable for the transformation of hematopoietic factor-dependent cell lines.
Skip Nav Destination
ARTICLES|
November 15, 1995
The SH2 domain of P210BCR/ABL is not required for the transformation of hematopoietic factor-dependent cells
RL Jr Ilaria,
RL Jr Ilaria
Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Search for other works by this author on:
RA Van Etten
RA Van Etten
Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Search for other works by this author on:
Blood (1995) 86 (10): 3897–3904.
Citation
RL Jr Ilaria, RA Van Etten; The SH2 domain of P210BCR/ABL is not required for the transformation of hematopoietic factor-dependent cells. Blood 1995; 86 (10): 3897–3904. doi: https://doi.org/10.1182/blood.V86.10.3897.bloodjournal86103897
Download citation file:
November 15 1995
Advertisement intended for health care professionals
Cited By
Advertisement intended for health care professionals
This feature is available to Subscribers Only
Sign In or Create an Account Close Modal