XK-related protein 5 (XKR5) is a novel negative regulator of KIT/D816V-mediated transformation

Jianmin Sun, Tine Thingholm, Peter Højrup, Lars Rönnstrand

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Abstract

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.

Original languageEnglish
Article number48
JournalOncogenesis
Volume7
Issue number6
Number of pages11
ISSN2157-9024
DOIs
Publication statusPublished - 18. Jun 2018

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Proteins
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Sun, Jianmin ; Thingholm, Tine ; Højrup, Peter ; Rönnstrand, Lars. / XK-related protein 5 (XKR5) is a novel negative regulator of KIT/D816V-mediated transformation. In: Oncogenesis. 2018 ; Vol. 7, No. 6.
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abstract = "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.",
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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.

In: Oncogenesis, Vol. 7, No. 6, 48, 18.06.2018.

Research output: Contribution to journalJournal articleResearchpeer-review

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T1 - XK-related protein 5 (XKR5) is a novel negative regulator of KIT/D816V-mediated transformation

AU - Sun, Jianmin

AU - Thingholm, Tine

AU - Højrup, Peter

AU - Rönnstrand, Lars

PY - 2018/6/18

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AB - 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.

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