Počet záznamů: 1  

Elucidation of protein interactions necessary for the maintenance of the BCR-ABL signaling complex

  1. 1.
    0533597 - ÚŽFG 2021 RIV CH eng J - Článek v odborném periodiku
    Gregor, T. - Kunová Bosáková, Michaela - Nita, Alexandru - Abraham, S. P. - Fafílek, Bohumil - Černohorský, N. H. - Ryneš, J. - Foldynová Trantírková, S. - Žáčková, D. - Mayer, J. - Trantírek, L. - Krejčí, Pavel
    Elucidation of protein interactions necessary for the maintenance of the BCR-ABL signaling complex.
    Cellular and Molecular Life Sciences. Roč. 77, č. 19 (2020), s. 3885-3903. ISSN 1420-682X. E-ISSN 1420-9071
    Grant CEP: GA MŠMT(CZ) EF16_019/0000729
    Institucionální podpora: RVO:67985904 ; RVO:61388963
    Klíčová slova: BCR-ABL * chronic myeloid leukemia * signaling * protein complex
    Obor OECD: Developmental biology
    Impakt faktor: 9.261, rok: 2020
    Způsob publikování: Omezený přístup
    https://asep.lib.cas.cz/arl-cav/cs/csg/?repo=crepo1&key=40768217680

    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.
    Trvalý link: http://hdl.handle.net/11104/0311941

     
     
Počet záznamů: 1  

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