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Mycobacterial phosphatase PstP regulates global serine threonine phosphorylation and cell division.

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posted on 10.06.2019, 13:12 by Iswahyudi, GV Mukamolova, AA Straatman-Iwanowska, N Allcock, P Ajuh, O Turapov, HM O'Hare
Protein phosphatase PstP is conserved throughout the Actinobacteria in a genetic locus related to cell wall synthesis and cell division. In many Actinobacteria it is the sole annotated serine threonine protein phosphatase to counter the activity of multiple serine threonine protein kinases. We used transcriptional knockdown, electron microscopy and comparative phosphoproteomics to investigate the putative dual functions of PstP as a specific regulator of cell division and as a global regulator of protein phosphorylation. Comparative phosphoproteomics in the early stages of PstP depletion showed hyperphosphorylation of protein kinases and their substrates, confirming PstP as a negative regulator of kinase activity and global serine and threonine phosphorylation. Analysis of the 838 phosphorylation sites that changed significantly, suggested that PstP may regulate diverse phosphoproteins, preferentially at phosphothreonine near acidic residues, near the protein termini, and within membrane associated proteins. Increased phosphorylation of the activation loop of protein kinase B (PknB) and of the essential PknB substrate CwlM offer possible explanations for the requirement for pstP for growth and for cell wall defects when PstP was depleted.

Funding

Funding was provided by the BBSRC (BB/P001513/1) and the Indonesian Ministry of Education and Culture Direktorat Jenderal Pendidikan Tinggi (DIKTI). We would like to thank the University of Leicester Core Biotechnology Services Electron Microscopy Facility and Dr Maria Viskaduraki, Bioinformatics and Biostatistics Hub, for advice and suggestions on this work.

History

Citation

Scientific Reports, 2019, 9, Article number: 8337

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Infection, Immunity and Inflammation

Version

VoR (Version of Record)

Published in

Scientific Reports

Publisher

Nature Research (part of Springer Nature)

eissn

2045-2322

Acceptance date

24/05/2019

Copyright date

2019

Available date

10/06/2019

Publisher version

https://www.nature.com/articles/s41598-019-44841-9

Notes

The datasets generated during the current study are available in PRIDE, accession number: PXD011805. https://www.ebi.ac.uk/pride/archive/login.

Language

en

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