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PRL2 Phosphatase Promotes Oncogenic KIT Signaling in Leukemia Cells through Modulating CBL Phosphorylation

Chen, Hongxia ; Bai, Yunpeng ; Kobayashi, Michihiro ; Xiao, Shiyu ; Barajas, Sergio ; Cai, Wenjie ; Chen, Sisi ; Miao, Jinmin ; Meke, Frederick Nguele and Yao, Chonghua , et al. (2024) In Molecular Cancer Research 22(1). p.94-103
Abstract

Receptor tyrosine kinase KIT is frequently activated in acute myeloid leukemia (AML). While high PRL2 (PTP4A2) expression is correlated with activation of SCF/KIT signaling in AML, the underlying mechanisms are not fully understood. We discovered that inhibition of PRL2 significantly reduces the burden of oncogenic KIT-driven leukemia and extends leukemic mice survival. PRL2 enhances oncogenic KIT signaling in leukemia cells, promoting their proliferation and survival. We found that PRL2 dephosphorylates CBL at tyrosine 371 and inhibits its activity toward KIT, leading to decreased KIT ubiquitination and enhanced AKT and ERK signaling in leukemia cells.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular Cancer Research
volume
22
issue
1
pages
10 pages
publisher
American Association for Cancer Research
external identifiers
  • pmid:37756563
  • scopus:85181542813
ISSN
1541-7786
DOI
10.1158/1541-7786.MCR-23-0115
language
English
LU publication?
yes
id
abbd18ad-fc8f-48b1-af50-6d8a1802f25f
date added to LUP
2024-02-13 12:22:31
date last changed
2024-04-14 23:11:13
@article{abbd18ad-fc8f-48b1-af50-6d8a1802f25f,
  abstract     = {{<p>Receptor tyrosine kinase KIT is frequently activated in acute myeloid leukemia (AML). While high PRL2 (PTP4A2) expression is correlated with activation of SCF/KIT signaling in AML, the underlying mechanisms are not fully understood. We discovered that inhibition of PRL2 significantly reduces the burden of oncogenic KIT-driven leukemia and extends leukemic mice survival. PRL2 enhances oncogenic KIT signaling in leukemia cells, promoting their proliferation and survival. We found that PRL2 dephosphorylates CBL at tyrosine 371 and inhibits its activity toward KIT, leading to decreased KIT ubiquitination and enhanced AKT and ERK signaling in leukemia cells.</p>}},
  author       = {{Chen, Hongxia and Bai, Yunpeng and Kobayashi, Michihiro and Xiao, Shiyu and Barajas, Sergio and Cai, Wenjie and Chen, Sisi and Miao, Jinmin and Meke, Frederick Nguele and Yao, Chonghua and Yang, Yuxia and Strube, Katherine and Satchivi, Odelia and Sun, Jianmin and Ronnstrand, Lars and Croop, James M. and Boswell, H. Scott and Jia, Yuzhi and Liu, Huiping and Li, Loretta S. and Altman, Jessica K. and Eklund, Elizabeth A. and Sukhanova, Madina and Ji, Peng and Tong, Wei and Band, Hamid and Huang, Danny T. and Platanias, Leonidas C. and Zhang, Zhong Yin and Liu, Yan}},
  issn         = {{1541-7786}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{94--103}},
  publisher    = {{American Association for Cancer Research}},
  series       = {{Molecular Cancer Research}},
  title        = {{PRL2 Phosphatase Promotes Oncogenic KIT Signaling in Leukemia Cells through Modulating CBL Phosphorylation}},
  url          = {{http://dx.doi.org/10.1158/1541-7786.MCR-23-0115}},
  doi          = {{10.1158/1541-7786.MCR-23-0115}},
  volume       = {{22}},
  year         = {{2024}},
}