Serine threonine protein kinases of mycobacterial genus: phylogeny to function

Narayan, Azeet; Sachdeva, Preeti; Sharma, Kirti; Saini, Adesh K.; Tyagi, Anil K.; Singh, Yogendra

doi:10.1152/physiolgenomics.00221.2006

Cited by 82 publications

(79 citation statements)

References 70 publications

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“…First, multiple sequence alignment of bacterial GroEL homologues showed that several positions in the M. tuberculosis GroELs' equatorial domains were altered from different residues to serine/threonine, indicating potential phosphorylation sites (40,41). Second, the M. tuberculosis genome encodes 11 eukaryotic-like serine/threonine kinases (ELKs), and emerging evidence that ELKs play a role in different cellular processes, including stress adaptation, across bacterial genera tempted us to speculate that there is a role for ELKs in GroEL oligomerization (38,61,65). Third, some heat shock proteins, including mitochondrial and chloroplast Hsp60 homologues, exhibit heat-induced or concentration-dependent oligomerization.…”

Section: Mycobacterial Groel1 Exists In Multiple Oligomeric Formsmentioning

confidence: 99%

Facilitated Oligomerization of Mycobacterial GroEL: Evidence for Phosphorylation-Mediated Oligomerization

Kumar¹,

Khare

Srikanth³

et al. 2009

J Bacteriol

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The distinctive feature of the GroES-GroEL chaperonin system in mediating protein folding lies in its ability to exist in a tetradecameric state, form a central cavity, and encapsulate the substrate via the GroES lid. However, recombinant GroELs of Mycobacterium tuberculosis are unable to act as effective molecular chaperones when expressed in Escherichia coli. We demonstrate here that the inability of M. tuberculosis GroEL1 to act as a functional chaperone in E. coli can be alleviated by facilitated oligomerization. The results of directed evolution involving random DNA shuffling of the genes encoding M. tuberculosis GroEL homologues followed by selection for functional entities suggested that the loss of chaperoning ability of the recombinant mycobacterial GroEL1 and GroEL2 in E. coli might be due to their inability to form canonical tetradecamers. This was confirmed by the results of domain-swapping experiments that generated M. tuberculosis-E. coli chimeras bearing mutually exchanged equatorial domains, which revealed that E. coli GroEL loses its chaperonin activity due to alteration of its oligomerization capabilities and vice versa for M. tuberculosis GroEL1. Furthermore, studying the oligomerization status of native GroEL1 from cell lysates of M. tuberculosis revealed that it exists in multiple oligomeric forms, including single-ring and double-ring variants. Immunochemical and mass spectrometric studies of the native M. tuberculosis GroEL1 revealed that the tetradecameric form is phosphorylated on serine-393, while the heptameric form is not, indicating that the switch between the singleand double-ring variants is mediated by phosphorylation.

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Section: Mycobacterial Groel1 Exists In Multiple Oligomeric Formsmentioning

confidence: 99%

Facilitated Oligomerization of Mycobacterial GroEL: Evidence for Phosphorylation-Mediated Oligomerization

Kumar¹,

Khare

Srikanth³

et al. 2009

J Bacteriol

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“…The conservation of genes coding for division and cell wall biogenesis (dcw gene cluster) in the 30kb locus encompassing PknL, the phylogenetic relatedness to PknB/PknA and the existence of homologs in Corynebacterium glutamicum with carboxy terminal PASTA domains, represent the biological line of evidence that implicates a role for PknL in regulating cell wall biogenesis (Narayan et al, 2007).…”

Section: Estimating Intracellular Glutamine and Glutamate Levels By Hmentioning

confidence: 99%

Involvement of Serine Threonine Protein Kinase, PknL, from Mycobacterium Tuberculosis H37Rv in Starvation Response of Mycobacteria

Lakshminarayan¹,

Rajaram²

2009

JMBT

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The adaptation to nutrient depletion in bacteria involves a highly organized series of intracellular events that enable them to adapt to starvation conditions. The regulatory effect of serine threonine protein kinase, PknL, from Mycobacterium tuberculosis strain H 37 Rv was investigated under nutrient deprived conditions that simulate circumstances leading to latency. Recombinant PknL was expressed in Mycobacterium smegmatis strain mc 2 155 in its wild type and mutant forms. In vitro growth kinetics experiments revealed that clone expressing active PknL had a significant growth advantage under nutrient limiting conditions. Experiments were conducted to ascertain the in silico predictions of the involvement of PknL in regulating glutamine metabolism in mycobacteria. Furthermore, a role for PknL in cell wall biogenesis/cell division was shown by scanning electron microscopy.

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“…Three main superfamilies of protein kinases are described as follows, the first one includes the "eukaryotic like" serine/threonine protein kinases (STPKs) (7)(8)(9); the second one corresponds to the newly characterized prokaryotic class of tyrosine kinases (10); and the third one corresponds to the well known family of bacterial kinases, the sensor histidine kinases, which are key enzymes of the so-called "two-component systems" (11). In bacteria, the presence of several STPKs suggests a central role of protein phosphorylation in regulating various biological functions, ranging from environmental adaptive responses to bacterial pathogenicity, like in the actinomycete relative Mycobacterium tuberculosis (12,13). Thus, regulatory devices involving STPKs and phosphatases represent an emerging theme in prokaryotic signaling cascades.…”

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From the Characterization of the Four Serine/Threonine Protein Kinases (PknA/B/G/L) of Corynebacterium glutamicum toward the Role of PknA and PknB in Cell Division

Fiuza

Canova

Zanella-Cléon

et al. 2008

Journal of Biological Chemistry

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Corynebacterium glutamicum contains four serine/threonine protein kinases (STPKs) named PknA, PknB, PknG, and PknL. Here we present the first biochemical and comparative analysis of all four C. glutamicum STPKs and investigate their potential role in cell shape control and peptidoglycan synthesis during cell division. In vitro assays demonstrated that, except for PknG, all STPKs exhibited autokinase activity. We provide evidence that activation of PknG is part of a phosphorylation cascade mechanism that relies on PknA activity. Following phosphorylation by PknA, PknG could transphosphorylate its specific substrate OdhI in vitro. A mass spectrometry profiling approach was also used to identify the phosphoresidues in all four STPKs. The results indicate that the nature, number, and localization of the phosphoacceptors varies from one kinase to the other. Disruption of either pknL or pknG in C. glutamicum resulted in viable mutants presenting a typical cell morphology and growth rate. In contrast, we failed to obtain null mutants of pknA or pknB, supporting the notion that these genes are essential. Conditional mutants of pknA or pknB were therefore created, leading to partial depletion of PknA or PknB. This resulted in elongated cells, indicative of a cell division defect. Moreover, overexpression of PknA or PknB in C. glutamicum resulted in a lack of apical growth and therefore a coccoid-like morphology. These findings indicate that pknA and pknB are key players in signal transduction pathways for the regulation of the cell shape and both are essential for sustaining corynebacterial growth.Corynebacterium glutamicum is a leading industrial amino acid producer and a model organism of the Corynebacteriaceae, a suborder of the actinomycetes that also includes the genus Mycobacterium. This soil-borne, nonpathogenic Grampositive actinomycete, which is widely used in the industrial production of amino acids, such as L-lysine and L-glutamic acid (1), has been extensively studied leading to the development of efficient genetic manipulation systems (3).The genetics of cell growth and cell division of C. glutamicum started even before the complete genome sequence was available. The earliest studies focused on the sequencing and characterization of corynebacterial genes present in the conserved division and cell wall cluster (2). Once the genome sequence was available, it was evident that this bacterium, as well as different members of the actinomycetes, was deficient in many essential genes for cell division (3) and therefore corresponded to a minimalist version of a more sophisticated cell division apparatus (divisome) present in other bacteria. For instance, C. glutamicum is lacking genes homologue to ftsA (an actin homologue), to positive regulators involved in FtsZ polymerization such as zipA or zapA, or to negative regulators such as ezrA, noc, slmA, sulA, and minCD (3). Moreover, several essential cell division genes (i.e. ftsN and ftsL) are absent in C. glutamicum. Unlike other bacterial models, peptidoglycan (PG) ...

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Serine threonine protein kinases of mycobacterial genus: phylogeny to function

Cited by 82 publications

References 70 publications

Facilitated Oligomerization of Mycobacterial GroEL: Evidence for Phosphorylation-Mediated Oligomerization

Facilitated Oligomerization of Mycobacterial GroEL: Evidence for Phosphorylation-Mediated Oligomerization

Involvement of Serine Threonine Protein Kinase, PknL, from Mycobacterium Tuberculosis H37Rv in Starvation Response of Mycobacteria

From the Characterization of the Four Serine/Threonine Protein Kinases (PknA/B/G/L) of Corynebacterium glutamicum toward the Role of PknA and PknB in Cell Division

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