Elucidation of protein interactions necessary for the maintenance of the BCR-ABL signaling complex
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F20%3A00533597" target="_blank" >RIV/61388963:_____/20:00533597 - isvavai.cz</a>
Alternative codes found
RIV/67985904:_____/20:00533597 RIV/00216224:14110/20:00116512 RIV/65269705:_____/20:00073337 RIV/00159816:_____/20:00073337
Result on the web
<a href="https://asep.lib.cas.cz/arl-cav/cs/csg/?repo=crepo1&key=40768217680" target="_blank" >https://asep.lib.cas.cz/arl-cav/cs/csg/?repo=crepo1&key=40768217680</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1007/s00018-019-03397-7" target="_blank" >10.1007/s00018-019-03397-7</a>
Alternative languages
Result language
angličtina
Original language name
Elucidation of protein interactions necessary for the maintenance of the BCR-ABL signaling complex
Original language description
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.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10605 - Developmental biology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Cellular and Molecular Life Sciences
ISSN
1420-682X
e-ISSN
—
Volume of the periodical
77
Issue of the periodical within the volume
19
Country of publishing house
CH - SWITZERLAND
Number of pages
19
Pages from-to
3885-3903
UT code for WoS article
000566036300001
EID of the result in the Scopus database
2-s2.0-85076367083