Phosphorylation of Mycobacterium tuberculosis Ser/Thr phosphatase by PknA and PknB |
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Authors: | Sajid Andaleeb Arora Gunjan Gupta Meetu Upadhyay Sandeep Nandicoori Vinay K Singh Yogendra |
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Institution: | Institute of Genomics and Integrative Biology (CSIR), Delhi, India. |
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Abstract: | BackgroundThe integrated functions of 11 Ser/Thr protein kinases (STPKs) and one
phosphatase manipulate the phosphorylation levels of critical proteins in
Mycobacterium tuberculosis. In this study, we show that
the lone Ser/Thr phosphatase (PstP) is regulated through phosphorylation by
STPKs.Principal FindingsPstP is phosphorylated by PknA and PknB and phosphorylation is influenced by
the presence of Zn2+-ions and inorganic phosphate (Pi). PstP
is differentially phosphorylated on the cytosolic domain with
Thr137, Thr141, Thr174 and
Thr290 being the target residues of PknB while
Thr137 and Thr174 are phosphorylated by PknA. The
Mn2+-ion binding residues Asp38 and
Asp229 are critical for the optimal activity of PstP and
substitution of these residues affects its phosphorylation status. Native
PstP and its phosphatase deficient mutant PstPc
D38G
are phosphorylated by PknA and PknB in E. coli and addition
of Zn2+/Pi in the culture conditions affect the
phosphorylation level of PstP. Interestingly, the phosphorylated phosphatase
is more active than its unphosphorylated equivalent.Conclusions and SignificanceThis study establishes the novel mechanisms for regulation of mycobacterial
Ser/Thr phosphatase. The results indicate that STPKs and PstP may regulate
the signaling through mutually dependent mechanisms. Consequently, PstP
phosphorylation may play a critical role in regulating its own activity.
Since, the equilibrium between phosphorylated and non-phosphorylated states
of mycobacterial proteins is still unexplained, understanding the regulation
of PstP may help in deciphering the signal transduction pathways mediated by
STPKs and the reversibility of the phenomena. |
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Keywords: | |
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