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. Li; Jessica K. Altman; Elizabeth A. Eklund; Madina Sukhanova; Peng Ji; Wei Tong; Hamid Band; Danny T. Huang; Leonidas C. Platanias; Zhong Yin Zhang; Yan Liu

doi:10.1158/1541-7786.MCR-23-0115

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

Research output: Contribution to journal › Article › peer-review

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 language	English
Pages (from-to)	94-103
Number of pages	10
Journal	Molecular Cancer Research
Volume	22
Issue number	1
DOIs	https://doi.org/10.1158/1541-7786.MCR-23-0115
Publication status	Published - 2024

Subject classification (UKÄ)

Cancer and Oncology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1158/1541-7786.MCR-23-0115

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Chen, H., Bai, Y., Kobayashi, M., Xiao, S., Barajas, S., Cai, W., Chen, S., Miao, J., Meke, F. N., Yao, C., Yang, Y., Strube, K., Satchivi, O., Sun, J., Ronnstrand, L., Croop, J. M., Boswell, H. S., Jia, Y., Liu, H., ... Liu, Y. (2024). PRL2 Phosphatase Promotes Oncogenic KIT Signaling in Leukemia Cells through Modulating CBL Phosphorylation. Molecular Cancer Research, 22(1), 94-103. https://doi.org/10.1158/1541-7786.MCR-23-0115

@article{abbd18adfc8f48b1af506d8a1802f25f,

title = "PRL2 Phosphatase Promotes Oncogenic KIT Signaling in Leukemia Cells through Modulating CBL Phosphorylation",

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.",

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

year = "2024",

doi = "10.1158/1541-7786.MCR-23-0115",

language = "English",

volume = "22",

pages = "94--103",

journal = "Molecular Cancer Research",

issn = "1541-7786",

publisher = "American Association for Cancer Research",

number = "1",

}

Chen, H, Bai, Y, Kobayashi, M, Xiao, S, Barajas, S, Cai, W, Chen, S, Miao, J, Meke, FN, Yao, C, Yang, Y, Strube, K, Satchivi, O, Sun, J, Ronnstrand, L, Croop, JM, Boswell, HS, Jia, Y, Liu, H, Li, LS, Altman, JK, Eklund, EA, Sukhanova, M, Ji, P, Tong, W, Band, H, Huang, DT, Platanias, LC, Zhang, ZY & Liu, Y 2024, 'PRL2 Phosphatase Promotes Oncogenic KIT Signaling in Leukemia Cells through Modulating CBL Phosphorylation', Molecular Cancer Research, vol. 22, no. 1, pp. 94-103. https://doi.org/10.1158/1541-7786.MCR-23-0115

TY - JOUR

T1 - PRL2 Phosphatase Promotes Oncogenic KIT Signaling in Leukemia Cells through Modulating CBL Phosphorylation

AU - Chen, Hongxia

AU - Bai, Yunpeng

AU - Kobayashi, Michihiro

AU - Xiao, Shiyu

AU - Barajas, Sergio

AU - Cai, Wenjie

AU - Chen, Sisi

AU - Miao, Jinmin

AU - Meke, Frederick Nguele

AU - Yao, Chonghua

AU - Yang, Yuxia

AU - Strube, Katherine

AU - Satchivi, Odelia

AU - Sun, Jianmin

AU - Ronnstrand, Lars

AU - Croop, James M.

AU - Boswell, H. Scott

AU - Jia, Yuzhi

AU - Liu, Huiping

AU - Li, Loretta S.

AU - Altman, Jessica K.

AU - Eklund, Elizabeth A.

AU - Sukhanova, Madina

AU - Ji, Peng

AU - Tong, Wei

AU - Band, Hamid

AU - Huang, Danny T.

AU - Platanias, Leonidas C.

AU - Zhang, Zhong Yin

AU - Liu, Yan

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85181542813

U2 - 10.1158/1541-7786.MCR-23-0115

DO - 10.1158/1541-7786.MCR-23-0115

M3 - Article

C2 - 37756563

AN - SCOPUS:85181542813

SN - 1541-7786

VL - 22

SP - 94

EP - 103

JO - Molecular Cancer Research

JF - Molecular Cancer Research

IS - 1

ER -

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

Abstract

Subject classification (UKÄ)

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