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

Hongxia Chen, Yunpeng Bai, Michihiro Kobayashi, Shiyu Xiao, Sergio Barajas, Wenjie Cai, Sisi Chen, Jinmin Miao, Frederick Nguele Meke, Chonghua Yao, Yuxia Yang, Katherine Strube, Odelia Satchivi, Jianmin Sun, Lars Ronnstrand, James M. Croop, H. Scott Boswell, Yuzhi Jia, Huiping Liu, Loretta S. LiJessica K. Altman, Elizabeth A. Eklund, Madina Sukhanova, Peng Ji, Wei Tong, Hamid Band, Danny T. Huang, Leonidas C. Platanias, Zhong Yin Zhang*, Yan Liu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)94-103
Number of pages10
JournalMolecular Cancer Research
Volume22
Issue number1
DOIs
StatePublished - Jan 2024

Funding

Y. Liu was supported by fundings from NIH (R01HL150624, R56DK119524, and R56AG052501), DoD (W81XWH-18–1-0265 and W81XWH-19–1-0575), the Leukemia &Lymphoma Society (Translational Research Program award 6581–20) and the St. Baldrick’s Foundation (Scholar Award). Y. Bai, J. Maio, F. Nguele Make, and Z. Zhang were supported by fundings from NIH (R01CA069202) and the Robert C. and Charlotte Anderson Chair Endowment. S. Barajas was supported by an F31 Award (F31HL160120) from NIH. H. Chen was supported by Natural Science Foundation of Chongqing, China (cstc2020jcyj-msxmX0969). The authors would like to thank the NUseq Core, Quantitative Data Science Core, Pathology Core, Flow Cytometry Core, and Imaging core at Northwestern University Feinberg School of Medicine and Robert H. Lurie Comprehensive Cancer Center. H. Liu reports other support from ExoMira Medicine and grants from NIH/NCI and NIAID, DOD, American Cancer Society, and Chicago Biomedical Consortium outside the submitted work. L.S. Li reports other support from Ajax Therapeutics outside the submitted work. J.K. Altman reports other support from BioSight, Agios,

ASJC Scopus subject areas

  • General Medicine

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