XK-related protein 5 (XKR5) is a novel negative regulator of KIT/D816V-mediated transformation
(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
- Sun, Jianmin LU ; Thingholm, Tine LU ; Højrup, Peter and Rönnstrand, Lars LU
- organization
- publishing date
- 2018-06-01
- 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}}, }