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Phosphorylation control of protein tyrosine phosphatase A activity in Mycobacterium tuberculosis

Peifu Zhou1, Wu Li2, Dennis Wong3

  • 1Department of Medicine, Division of Infectious Diseases, University of British Columbia, Vancouver, BC V5Z 3J5, Canada; Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-environment and Bio-resource of the Three Gorges Area, Key Laboratory of Eco-environment of Three Gorges Reservoir, Ministry of Education, School of Life Sciences, Southwest University, Chongqing 400715, China; Institute of Ethnic-minority Medicine, School of Chemistry & Environmental Science, Guizhou Minzu University, Guiyang 550025, China.

FEBS Letters
|December 24, 2014
PubMed

Insights

Mycobacterium tuberculosis (Mtb) protein tyrosine phosphatase A (PtpA) activity is enhanced by phosphorylation from two distinct protein kinase families. PtkA and PknA regulate PtpA, impacting Mtb pathogenesis.

Area of Science:

  • Microbiology
  • Biochemistry
  • Molecular Biology

Background:

  • Protein tyrosine phosphatase A (PtpA) is crucial for Mycobacterium tuberculosis (Mtb) macrophage infection.
  • Protein tyrosine kinase A (PtkA) was the first identified kinase to phosphorylate PtpA.

Purpose of the Study:

  • To investigate how PtkA and other kinases modulate PtpA activity.
  • To understand the regulatory mechanisms of PtpA in Mtb.

Main Methods:

  • In vitro phosphorylation assays to determine kinase targets and effects.
  • Ex-vivo protein-protein interaction assays to identify interacting kinases.
  • Analysis of specific phosphorylation sites (Tyr-128, Tyr-129, Thr-45).

Main Results:

  • PtkA-mediated phosphorylation of PtpA at Tyr-128 and Tyr-129 enhances its phosphatase activity.
  • Ex-vivo assays revealed PtpA is phosphorylated by eukaryotic-like Ser/Thr kinases, including protein kinase A (PknA).
  • PknA regulates PtpA activity via phosphorylation at Thr-45.

Conclusions:

  • Two independent families of protein kinases (tyrosine and Ser/Thr kinases) regulate PtpA activity in Mtb.
  • This dual kinase regulation provides a sophisticated mechanism to control PtpA function during infection.
Keywords:
Mycobacterium tuberculosisPhosphorylationProtein kinase AProtein tyrosine kinase AProtein tyrosine phosphatase A

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