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XK-related protein 5 (XKR5) is a novel negative regulator of KIT/D816V-mediated transformation.
Sun, Jianmin; Thingholm, Tine; Højrup, Peter; Rönnstrand, Lars.
Afiliación
  • Sun J; Department of Pathogen Biology and Immunology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, China.
  • Thingholm T; Department of Laboratory Medicine, Translational Cancer Research, Lund University, Lund, Sweden.
  • Højrup P; Department of Laboratory Medicine, Lund Stem Cell Center, Lund University, Lund, Sweden.
  • Rönnstrand L; Department of Laboratory Medicine, Translational Cancer Research, Lund University, Lund, Sweden.
Oncogenesis ; 7(6): 48, 2018 Jun 18.
Article en En | MEDLINE | ID: mdl-29910466
In order to investigate the molecular mechanisms by which the oncogenic mutant KIT/D816V causes transformation of cells, we investigated proteins that selectively bind KIT/D816V, but not wild-type KIT, as potential mediators of transformation. By mass spectrometry several proteins were identified, among them a previously uncharacterized protein denoted XKR5 (XK-related protein 5), which is related to the X Kell blood group proteins. We could demonstrate that interaction between XKR5 and KIT/D816V leads to phosphorylation of XKR5 at Tyr 369, Tyr487, and Tyr 543. Tyrosine phosphorylated XKR5 acts as a negative regulator of KIT signaling, which leads to downregulation of phosphorylation of ERK, AKT, and p38. This led to reduced proliferation and colony forming capacity in semi-solid medium. Taken together, our data demonstrate that XKR5 is a novel type of negative regulator of KIT-mediated transformation.

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Oncogenesis Año: 2018 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Oncogenesis Año: 2018 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos