M. tuberculosis Ser/Thr Protein Kinase D Phosphorylates an Anti-Anti–Sigma Factor Homolog

PLoS Pathogens

Christina E Baer¹  Jason A MacGurn²  Jeffery S Cox²  Andrew E Greenstein³  Tom Alber³  Arnold M Falick⁴ 

[1] Biophysics Graduate Group, University of California, Berkeley, California, United States of America;Department of Microbiology and Immunology, University of California San Francisco, San Francisco, California, United States of America;Department of Molecular and Cell Biology, University of California, Berkeley, California, United States of America;Howard Hughes Medical Institute Mass Spectrometry Laboratory, University of California, Berkeley, California, United States of America

关键词: Phosphorylation;    Mycobacterium tuberculosis;    Regulator genes;    Gene regulation;    In vitro kinase assay;    Bacillus subtilis;    Phosphatases;    Transcriptional control;   

DOI  :  10.1371/journal.ppat.0030049

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Receptor Ser/Thr protein kinases are candidates for sensors that govern developmental changes and disease processes of Mycobacterium tuberculosis (Mtb), but the functions of these kinases are not established. Here, we show that Mtb protein kinase (Pkn) D overexpression alters transcription of numerous bacterial genes, including Rv0516c, a putative anti-anti–sigma factor, and genes regulated by sigma factor F. The PknD kinase domain directly phosphorylated Rv0516c, but no other sigma factor regulator, in vitro. In contrast, the purified PknB and PknE kinase domains phosphorylated distinct sigma regulators. Rather than modifying a consensus site, PknD phosphorylated Rv0516c in vitro and in vivo on Thr2 in a unique N-terminal extension. This phosphorylation inhibited Rv0516c binding in vitro to a homologous anti-anti–sigma factor, Rv2638. These results support a model in which signals transmitted through PknD alter the transcriptional program of Mtb by stimulating phosphorylation of a sigma factor regulator at an unprecedented control site.

【 授权许可】

CC BY