Related Experiment Video
Updated: Feb 24, 2026

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors
Published on: July 17, 2020
The mycobacterial phosphatase PtpA regulates the expression of host genes and promotes cell proliferation
Jing Wang1, Pupu Ge1,2, Lihua Qiang1,3
1CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.
Abstract:
Mycobacterium tuberculosis PtpA is a secreted effector protein that dephosphorylates several proteins in the host cell cytoplasm, such as p-JNK, p-p38, and p-VPS33B, leading to suppression of host innate immunity. Here we show that, in addition, PtpA enters the nucleus of host cells and regulates the expression of host genes, some of which are known to be involved in host innate immunity or in cell proliferation and migration (such as GADD45A). PtpA can bind directly to the promoter region of GADD45A in vitro. Both phosphatase activity and DNA-binding ability of PtpA are important in suppressing host innate immune responses. Furthermore, PtpA-expressing Mycobacterium bovis BCG promotes proliferation and migration of human lung adenoma A549 cells in vitro and in a mouse xenograft model. Further research is needed to test whether mycobacteria, via PtpA, might affect cell proliferation or migration in humans. Mycobacterium tuberculosis secretes a protein, PtpA, that dephosphorylates proteins in the host cell cytoplasm, weakening immune responses. Here, the authors show that PtpA also enters the nucleus, affects the expression of several host genes, and promotes proliferation and migration of a cancer cell line.
Insights
Mycobacterium tuberculosis PtpA protein suppresses host immunity by dephosphorylating cytoplasmic proteins. It also enters the nucleus, altering gene expression and promoting cancer cell proliferation and migration.
Area of Science:
- Microbiology
- Cell Biology
- Immunology
Background:
- Mycobacterium tuberculosis secretes PtpA, an effector protein.
- PtpA dephosphorylates host cytoplasmic proteins, suppressing innate immunity.
Purpose of the Study:
- Investigate PtpA's nuclear functions.
- Determine PtpA's role in host gene expression and cell behavior.
Main Methods:
- Studied PtpA's localization within host cells.
- Analyzed PtpA's effect on host gene expression.
- Assessed PtpA's impact on cell proliferation and migration in vitro and in vivo.
Main Results:
- PtpA enters the host cell nucleus.
- PtpA regulates host gene expression, including GADD45A.
- PtpA binds to the GADD45A promoter.
- PtpA promotes cancer cell proliferation and migration.
Conclusions:
- PtpA possesses nuclear functions beyond cytoplasmic dephosphorylation.
- Both phosphatase activity and DNA-binding are crucial for PtpA's immune suppression.
- PtpA may influence cell proliferation and migration, with potential implications for human diseases.
Related Concept Videos
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
Abnormal Proliferation
PI3K/mTOR/AKT Signaling Pathway
Stringent Response in E. coli
The JAK-STAT Signaling Pathway
TGF - β Signaling Pathway

