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@article{1681537,
author = {Gregor, Tomáš and Bosáková, Michaela and Nită, Alexandru and Poovakulathu Abraham, Sara and Fafílek, Bohumil and Černohorská, Nicole and Ryneš, Jan and Trantírková, Silvie and Žáčková, Daniela and Mayer, Jiří and Trantírek, Lukáš and Krejčí, Pavel},
article_location = {BASEL},
article_number = {19},
doi = {http://dx.doi.org/10.1007/s00018-019-03397-7},
keywords = {BCR-ABL; Chronic myeloid leukemia; Signaling; Protein complex},
language = {eng},
issn = {1420-682X},
journal = {Cellular and molecular life sciences},
title = {Elucidation of protein interactions necessary for the maintenance of the BCR-ABL signaling complex},
url = {https://link.springer.com/article/10.1007/s00018-019-03397-7},
volume = {77},
year = {2020}
}
TY - JOUR
ID - 1681537
AU - Gregor, Tomáš - Bosáková, Michaela - Nită, Alexandru - Poovakulathu Abraham, Sara - Fafílek, Bohumil - Černohorská, Nicole - Ryneš, Jan - Trantírková, Silvie - Žáčková, Daniela - Mayer, Jiří - Trantírek, Lukáš - Krejčí, Pavel
PY - 2020
TI - Elucidation of protein interactions necessary for the maintenance of the BCR-ABL signaling complex
JF - Cellular and molecular life sciences
VL - 77
IS - 19
SP - 3885-3903
EP - 3885-3903
PB - SPRINGER BASEL AG
SN - 1420682X
KW - BCR-ABL
KW - Chronic myeloid leukemia
KW - Signaling
KW - Protein complex
UR - https://link.springer.com/article/10.1007/s00018-019-03397-7
L2 - https://link.springer.com/article/10.1007/s00018-019-03397-7
N2 - Many patients with chronic myeloid leukemia in deep remission experience return of clinical disease after withdrawal of tyrosine kinase inhibitors (TKIs). This suggests signaling of inactive BCR-ABL, which allows the survival of cancer cells, and relapse. We show that TKI treatment inhibits catalytic activity of BCR-ABL, but does not dissolve BCR-ABL core signaling complex, consisting of CRKL, SHC1, GRB2, SOS1, cCBL, p85a-PI3K, STS1 and SHIP2. Peptide microarray and co-immunoprecipitation results demonstrate that CRKL binds to proline-rich regions located in C-terminal, intrinsically disordered region of BCR-ABL, that SHC1 requires pleckstrin homology, src homology and tyrosine kinase domains of BCR-ABL for binding, and that BCR-ABL sequence motif located in disordered region around phosphorylated tyrosine 177 mediates binding of three core complex members, i.e., GRB2, SOS1, and cCBL. Further, SHIP2 binds to the src homology and tyrosine kinase domains of BCR-ABL and its inositol phosphatase activity contributes to BCR-ABL-mediated phosphorylation of SHC1. Together, this study characterizes protein-protein interactions within the BCR-ABL core complex and determines the contribution of particular BCR-ABL domains to downstream signaling. Understanding the structure and dynamics of BCR-ABL interactome is critical for the development of drugs targeting integrity of the BCR-ABL core complex.
ER -
GREGOR, Tomáš, Michaela BOSÁKOVÁ, Alexandru NIT$\backslash$U A, Sara POOVAKULATHU ABRAHAM, Bohumil FAFÍLEK, Nicole ČERNOHORSKÁ, Jan RYNEŠ, Silvie TRANTÍRKOVÁ, Daniela ŽÁČKOVÁ, Jiří MAYER, Lukáš TRANTÍREK and Pavel KREJČÍ. Elucidation of protein interactions necessary for the maintenance of the BCR-ABL signaling complex. \textit{Cellular and molecular life sciences}. BASEL: SPRINGER BASEL AG, vol.~77, No~19, p.~3885-3903. ISSN~1420-682X. doi:10.1007/s00018-019-03397-7. 2020.
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