TY - JOUR
T1 - Transforming properties of the huntingtin interacting protein 1/platelet-derived growth factor β receptor fusion protein
AU - Ross, Theodora S.
AU - Gilliland, D. Gary
PY - 1999/8/6
Y1 - 1999/8/6
N2 - We have previously reported that the Huntingtin interacting protein 1 (HIP1) gene is fused to the platelet-derived growth factor β receptor (PDGFβR) gene in a patient with chronic myelomonocytic leukemia. We now show that HIP1/PDGFβR oligomerizes, is constitutively tyrosine-phosphorylated, and transforms the murine hematopoietic cell line, Ba/F3, to interleukin-3- independent growth. A kinase-inactive mutant is neither tyrosine- phosphorylated nor able to transform Ba/F3 cells. Oligomerization and kinase activation required the 55-amino acid carboxyl-terminal TALIN homology region but not the leucine zipper domain. Tyrosine phosphorylation of a 130-kDa protein and STAT5 correlates with transformation in cells expressing HIP1/PDGFβR and related mutants. A deletion mutant fusion protein that contains only the TALIN homology region of HIP1 fused to PDGFβR is incapable of transforming Ba/F3 cells and does not tyrosine-phosphorylate p130 or STAT5, although it is itself constitutively tyrosine-phosphorylated. We have also analyzed cells expressing Tyr → Phe mutants of HIP1/PDGFβR in the known PDGFβR SH2 docking sites and report that none of these sites are necessary for STAT5 activation, p130 phosphorylation, or Ba/F3 transformation. The correlation of factor-independent growth of hematopoietic cells with p130 and STAT5 phosphorylation/activation in both the HIP1/PDGFβR Tyr → Phe and deletion mutational variants suggests that both STAT5 and p130 are important for transformation mediated by HIP1/PDGFβR.
AB - We have previously reported that the Huntingtin interacting protein 1 (HIP1) gene is fused to the platelet-derived growth factor β receptor (PDGFβR) gene in a patient with chronic myelomonocytic leukemia. We now show that HIP1/PDGFβR oligomerizes, is constitutively tyrosine-phosphorylated, and transforms the murine hematopoietic cell line, Ba/F3, to interleukin-3- independent growth. A kinase-inactive mutant is neither tyrosine- phosphorylated nor able to transform Ba/F3 cells. Oligomerization and kinase activation required the 55-amino acid carboxyl-terminal TALIN homology region but not the leucine zipper domain. Tyrosine phosphorylation of a 130-kDa protein and STAT5 correlates with transformation in cells expressing HIP1/PDGFβR and related mutants. A deletion mutant fusion protein that contains only the TALIN homology region of HIP1 fused to PDGFβR is incapable of transforming Ba/F3 cells and does not tyrosine-phosphorylate p130 or STAT5, although it is itself constitutively tyrosine-phosphorylated. We have also analyzed cells expressing Tyr → Phe mutants of HIP1/PDGFβR in the known PDGFβR SH2 docking sites and report that none of these sites are necessary for STAT5 activation, p130 phosphorylation, or Ba/F3 transformation. The correlation of factor-independent growth of hematopoietic cells with p130 and STAT5 phosphorylation/activation in both the HIP1/PDGFβR Tyr → Phe and deletion mutational variants suggests that both STAT5 and p130 are important for transformation mediated by HIP1/PDGFβR.
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U2 - 10.1074/jbc.274.32.22328
DO - 10.1074/jbc.274.32.22328
M3 - Article
C2 - 10428802
AN - SCOPUS:0033529599
SN - 0021-9258
VL - 274
SP - 22328
EP - 22336
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 32
ER -