Modulation of Yeast Sln1 Kinase Activity by the Ccw12 Cell Wall Protein

Narang, Sandhya S.; Malone, Cheryl L.; Deschenes, Robert J.; Fassler, Jan S.

doi:10.1074/jbc.m706877200

Cited by 28 publications

(20 citation statements)

References 45 publications

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“…The active involvement of histidine kinases in the cell wall stress response was already demonstrated in S. cerevisiae (37). This hypothesis is suggested by the decrease in the total number of differentially expressed genes detected by using the two drugs in combination in comparison to the response induced by CAS alone.…”

Section: Discussionmentioning

confidence: 72%

Hitting the Caspofungin Salvage Pathway of Human-Pathogenic Fungi with the Novel Lasso Peptide Humidimycin (MDN-0010)

Valiante

Monteiro

Martín

et al. 2015

Antimicrob Agents Chemother

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f Fungal infections have increased dramatically in the last 2 decades, and fighting infectious diseases requires innovative approaches such as the combination of two drugs acting on different targets or even targeting a salvage pathway of one of the drugs. The fungal cell wall biosynthesis is inhibited by the clinically used antifungal drug caspofungin. This antifungal activity has been found to be potentiated by humidimycin, a new natural product identified from the screening of a collection of 20,000 microbial extracts, which has no major effect when used alone. An analysis of transcriptomes and selected Aspergillus fumigatus mutants indicated that humidimycin affects the high osmolarity glycerol response pathway. By combining humidimycin and caspofungin, a strong increase in caspofungin efficacy was achieved, demonstrating that targeting different signaling pathways provides an excellent basis to develop novel anti-infective strategies.

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Section: Discussionmentioning

confidence: 72%

Hitting the Caspofungin Salvage Pathway of Human-Pathogenic Fungi with the Novel Lasso Peptide Humidimycin (MDN-0010)

Valiante

Monteiro

Martín

et al. 2015

Antimicrob Agents Chemother

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“…Nevertheless, Cbk1 might control Golgi enzyme expression independently of Ace2. Indeed, Och1 mannosyltransferase expression is induced by HOG pathway inactivation and is enhanced in RAM deletion mutants, likely as a consequence of cell wall integrity pathway activation Narang et al, 2008). Nonetheless, Och1 induction alone cannot account for the diminished glycosylation of invertase and Sim1 in conditional cbk1 mutants.…”

Section: Cbk1 and Golgi Functionmentioning

confidence: 99%

The Yeast LATS/Ndr Kinase Cbk1 Regulates Growth via Golgi-dependent Glycosylation and Secretion

Kurischko

Kuravi

Wannissorn

et al. 2008

MBoC

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Saccharomyces cerevisiae Cbk1 is a LATS/Ndr protein kinase and a downstream component of the regulation of Ace2 and morphogenesis (RAM) signaling network. Cbk1 and the RAM network are required for cellular morphogenesis, cell separation, and maintenance of cell integrity. Here, we examine the phenotypes of conditional cbk1 mutants to determine the essential function of Cbk1. Cbk1 inhibition severely disrupts growth and protein secretion, and triggers the Swe1-dependent morphogenesis checkpoint. Cbk1 inhibition also delays the polarity establishment of the exocytosis regulators Rab-GTPase Sec4 and its exchange factor Sec2, but it does not interfere with actin polarity establishment. Cbk1 binds to and phosphorylates Sec2, suggesting that it regulates Sec4-dependent exocytosis. Intriguingly, Cbk1 inhibition causes a >30% decrease in post-Golgi vesicle accumulation in late secretion mutants, indicating that Cbk1 also functions upstream of Sec2-Sec4, perhaps at the level of the Golgi. In agreement, conditional cbk1 mutants mislocalize the cis-Golgi mannosyltransferase Och1, are hypersensitive to the aminoglycoside hygromycin B, and exhibit diminished invertase and Sim1 glycosylation. Significantly, the conditional lethality and hygromycin B sensitivity of cbk1 mutants are suppressed by moderate overexpression of several Golgi mannosyltransferases. These data suggest that an important function for Cbk1 and the RAM signaling network is to regulate growth and secretion via Golgi and Sec2/Sec4-dependent processes. INTRODUCTIONCell polarity is a common cellular feature among eukaryotic cells that is characterized by asymmetry in cell shape, protein distribution, and cellular function (Nelson, 2003;Pruyne et al., 2004). The establishment and maintenance of polarized growth are critical for the development and function of specialized cells, tissues, and organs. Polarized growth is particularly important for the development and function of neuronal cells, which can reach several meters in length, and for epithelial cells, which regulate homeostasis and maintain physical barriers between biological compartments (Arimura and Kaibuchi, 2005;Dow and Humbert, 2007;Tang, 2008). Dynamic changes in cell polarity are essential for cell migration during cell and tissue development. Polarized growth and morphogenesis are also important for yeast and filamentous fungi development (Harris, 2006).Saccharomyces cerevisiae is an excellent model organism for studying conserved mechanisms of polarized growth and cell division. Saccharomyces cerevisiae cells undergo polarized growth during cell division, mating, and pseudohyphae formation (Pruyne et al., 2004). Many of the evolutionarily conserved elements of cell growth and proliferation were first identified and characterized in yeast (Pruyne et al., 2004). Yeast polarity establishment involves the recruitment and activation of Cdc42 GTPase to a cortical landmark. Cdc42 regulates several polarity processes, including septin assembly and actin cytoskeleton polarization (Park and Bi, 2007). Po...

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“…In yeast, even though Sln1p has a similar HK domain organization to the bacterial osmosensor EnvZ [6,13], there is no evidence of a direct effect of osmotic imbalance on Sln1p structure. On the other hand, Sln1p (i) has a kinase activity enhanced by increased glycerol intracellular concentration [14]; (ii) responds to changes in turgor pressure [15]; (iii) is able to respond to changes induced by osmolarity in the cell wall [16] and (iv) its dimerization is disrupted by the osmotic stress leading to the inactivation of the kinase [17]. Finally, the importance of Sln1p in osmosensing has been extensively demonstrated even if, conversely to EnvZ, the structural mechanism of the kinase activation is not clearly established.…”

Section: Introductionmentioning

confidence: 99%

Functional Divergence of Poplar Histidine-Aspartate Kinase HK1 Paralogs in Response to Osmotic Stress

Héricourt

Chefdor

Djeghdir

et al. 2016

IJMS

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Previous works have shown the existence of protein partnerships belonging to a MultiStep Phosphorelay (MSP) in Populus putatively involved in osmosensing. This study is focused on the identification of a histidine-aspartate kinase, HK1b, paralog of HK1a. The characterization of HK1b showed its ability to homo- and hetero-dimerize and to interact with a few Histidine-containing Phosphotransfer (HPt) proteins, suggesting a preferential partnership in poplar MSP linked to drought perception. Furthermore, determinants for interaction specificity between HK1a/1b and HPts were studied by mutagenesis analysis, identifying amino acids involved in this specificity. The HK1b expression analysis in different poplar organs revealed its co-expression with three HPts, reinforcing the hypothesis of partnership participation in the MSP in planta. Moreover, HK1b was shown to act as an osmosensor with kinase activity in a functional complementation assay of an osmosensor deficient yeast strain. These results revealed that HK1b showed a different behaviour for canonical phosphorylation of histidine and aspartate residues. These phosphorylation modularities of canonical amino acids could explain the improved osmosensor performances observed in yeast. As conserved duplicates reflect the selective pressures imposed by the environmental requirements on the species, our results emphasize the importance of HK1 gene duplication in poplar adaptation to drought stress.

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Modulation of Yeast Sln1 Kinase Activity by the Ccw12 Cell Wall Protein

Cited by 28 publications

References 45 publications

Hitting the Caspofungin Salvage Pathway of Human-Pathogenic Fungi with the Novel Lasso Peptide Humidimycin (MDN-0010)

Hitting the Caspofungin Salvage Pathway of Human-Pathogenic Fungi with the Novel Lasso Peptide Humidimycin (MDN-0010)

The Yeast LATS/Ndr Kinase Cbk1 Regulates Growth via Golgi-dependent Glycosylation and Secretion

Functional Divergence of Poplar Histidine-Aspartate Kinase HK1 Paralogs in Response to Osmotic Stress

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