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

Sun, Jianmin LU ; Thingholm, Tine LU ; Højrup, Peter and Rönnstrand, Lars LU orcid (2018) In Oncogenesis 7(6).
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... (More)

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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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Oncogenesis
volume
7
issue
6
article number
00573
publisher
Nature Publishing Group
external identifiers
  • scopus:85048705037
  • pmid:29910466
ISSN
2157-9024
DOI
10.1038/s41389-018-0057-3
language
English
LU publication?
yes
id
f0db0541-9fc5-4aae-92ea-95dfb10d688a
date added to LUP
2018-06-29 14:17:07
date last changed
2024-06-24 16:29:35
@article{f0db0541-9fc5-4aae-92ea-95dfb10d688a,
  abstract     = {{<p>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.</p>}},
  author       = {{Sun, Jianmin and Thingholm, Tine and Højrup, Peter and Rönnstrand, Lars}},
  issn         = {{2157-9024}},
  language     = {{eng}},
  month        = {{06}},
  number       = {{6}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Oncogenesis}},
  title        = {{XK-related protein 5 (XKR5) is a novel negative regulator of KIT/D816V-mediated transformation}},
  url          = {{http://dx.doi.org/10.1038/s41389-018-0057-3}},
  doi          = {{10.1038/s41389-018-0057-3}},
  volume       = {{7}},
  year         = {{2018}},
}