Cbk1 kinase and Bck2 control MAP kinase activation and inactivation during heat shock

Kuravi, Venkata K.; Kurischko, Cornelia; Puri, Manasi; Luca, Francis C.

doi:10.1091/mbc.e11-04-0371

Cited by 21 publications

(27 citation statements)

References 80 publications

(173 reference statements)

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“…The RAM network has been most extensively studied in S. cerevisiae and has been implicated in the regulation of a number of cellular processes, including mother-daughter cell separation (3,18,65,69), daughter cell-specific gene transcription (12,81), maintenance of cell wall integrity (18,50,77), cell cycle progression (4,7,70), mating projection formation and mating efficiency (3,5,65,81), polarized growth (18,65,69,81), and stress signaling (47). As detailed in this review, many of the functions of the RAM pathway characterized in S. cerevisiae are conserved in other model and pathogenic fungi.…”

Section: Overview Of Ram Pathwaymentioning

confidence: 99%

“…To date, only two ScCbk1 substrates have been well characterized: the zinc finger transcription factor ScAce2 (8,15) and the mRNA binding protein ScSsd1 (38,49,50). There is additional evidence suggesting that ScCbk1 may also regulate several other proteins, including the mRNA-binding protein ScPuf5/Mpt5 (5), the RAB GEF ScSec2 (51), and the cell wall integrity (CWI) pathway MAPKK ScBck2 (47).…”

Section: Overview Of Ram Pathwaymentioning

confidence: 99%

“…ScSsd1 associates with a subset of mRNAs involved in cell wall biosynthesis and cell growth, including the transcripts of several genes known to be dosage suppressors of Sccbk1 mutants (37,47,48). ScCbk1 binds to and phosphorylates ScSsd1, thereby influencing the subcellular distribution and translation of ScSsd1-mRNA complexes (37,48,49).…”

Section: Overview Of Ram Pathwaymentioning

confidence: 99%

“…In the absence of ScCbk1 activity, translation of ScSsd1-associated mRNAs is repressed (37). Recent data indicate that ScCbk1 also influences cell wall integrity during heat shock and cell wall stress via the cell wall integrity (CWI) signaling pathway (47). The CWI pathway is a MAP kinase cascade that regulates cell wall biosynthesis and cell wall stress responses (52).…”

Section: Overview Of Ram Pathwaymentioning

confidence: 99%

“…The CWI pathway is a MAP kinase cascade that regulates cell wall biosynthesis and cell wall stress responses (52). During heat shock and cell wall stress, ScCbk1 is critical for the activation but not the ScMkk1/Mkk2-dependent T190/Y192 phosphorylation of ScMpk1, the terminal MAP kinase of the CWI pathway (47). ScCbk1 also appears to regulate CWI pathway inactivation through the dual-specificity phosphatase ScSpd1 (52).…”

Section: Overview Of Ram Pathwaymentioning

confidence: 99%

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The RAM Network in Pathogenic Fungi

et al. 2012

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The regulation of Ace2 and morphogenesis (RAM) network is a protein kinase signaling pathway conserved among eukaryotes from yeasts to humans. Among fungi, the RAM network has been most extensively studied in the model yeast Saccharomyces cerevisiae and has been shown to regulate a range of cellular processes, including daughter cell-specific gene expression, cell cycle regulation, cell separation, mating, polarized growth, maintenance of cell wall integrity, and stress signaling. Increasing numbers of recent studies on the role of the RAM network in pathogenic fungal species have revealed that this network also plays an important role in the biology and pathogenesis of these organisms. In addition to providing a brief overview of the RAM network in S. cerevisiae, we summarize recent developments in the understanding of RAM network function in the human fungal pathogens Candida albicans, Candida glabrata, Cryptococcus neoformans, Aspergillus fumigatus, and Pneumocystis spp. Awide variety of key physiological processes in eukaryotic cells are regulated by networks of protein kinase-based signaling pathways. Accordingly, the study of these pathways has been the focus of intense research efforts in nearly every area of eukaryotic cell biology. Because a large number of protein kinase signaling pathways and cascades are highly conserved between model organisms and humans, our current understanding of many mechanistic paradigms for protein kinase-based cell signaling has developed from studies of model organisms, such as the budding yeast Saccharomyces cerevisiae (10). These studies not only have contributed to our fundamental understanding of eukaryotic biology but also have had profound biomedical implications (28). For example, protein kinases are frequently dysregulated in cancer cells, and consequently, protein kinase inhibitors such as imatinib have emerged as important components of current anticancer therapies (19).A second area of eukaryotic biology with important biomedical relevance that has benefited from S. cerevisiae-based studies of protein kinase signaling pathways is the study of pathogenic fungi (26,45). The ability of modern medicine to support patients with compromised immune function and the development of immunomodulatory therapies have contributed to an increase in the morbidity and mortality attributable to invasive fungal infections (14). As the medical importance of pathogenic fungi has increased, so too has interest in the fundamental biology of these organisms as well as the mechanistic basis of their pathogenesis (68). As a result, the study of protein kinase signaling networks has led to many important insights into fungal virulence, host-pathogen interactions, and, more recently, new approaches to antifungal therapy (1).An excellent example of a signaling pathway that is highly conserved within all eukaryotes, is well-studied in S. cerevisiae, and is currently being characterized in pathogenic fungi is the regulation of Ace2 and morphogenesis (RAM) network (65). In this minireview, we s...

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Section: Overview Of Ram Pathwaymentioning

confidence: 99%

Section: Overview Of Ram Pathwaymentioning

confidence: 99%

Section: Overview Of Ram Pathwaymentioning

confidence: 99%

Section: Overview Of Ram Pathwaymentioning

confidence: 99%

Section: Overview Of Ram Pathwaymentioning

confidence: 99%

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The RAM Network in Pathogenic Fungi

et al. 2012

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A walk-through MAPK structure and functionality with the 30-year-old yeast MAPK Slt2

et al. 2021

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Regulation of biotic interactions and responses to abiotic stresses by MAP kinase pathways in plant pathogenic fungi

et al. 2021

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Like other eukaryotes, fungi use MAP kinase (MAPK) pathways to mediate cellular changes responding to external stimuli. In the past two decades, three well-conserved MAP kinase pathways have been characterized in various plant pathogenic fungi for regulating responses and adaptations to a variety of biotic and abiotic stresses encountered during plant infection or survival in nature. The invasive growth (IG) pathway is homologous to the yeast pheromone response and filamentation pathways. In plant pathogens, the IG pathway often is essential for pathogenesis by regulating infection-related morphogenesis, such as appressorium formation, penetration, and invasive growth. The cell wall integrity (CWI) pathway also is important for plant infection although the infection processes it regulates vary among fungal pathogens. Besides its universal function in cell wall integrity, it often plays a minor role in responses to oxidative and cell wall stresses. Both the IG and CWI pathways are involved in regulating known virulence factors as well as effector genes during plant infection and mediating defenses against mycoviruses, bacteria, and other fungi. In contrast, the high osmolarity growth (HOG) pathway is dispensable for virulence in some fungi although it is essential for plant infection in others. It regulates osmoregulation in hyphae and is dispensable for appressorium turgor generation. The HOG pathway also plays a major role for responding to oxidative, heat, and other environmental stresses and is overstimulated by phenylpyrrole fungicides. Moreover, these three MAPK pathways crosstalk and coordinately regulate responses to various biotic and abiotic stresses. The IG and CWI pathways, particularly the latter, also are involved in responding to abiotic stresses to various degrees in different fungal pathogens, and the HOG pathway also plays a role in interactions with other microbes or fungi. Furthermore, some infection processes or stress responses are co-regulated by MAPK pathways with cAMP or Ca2+/CaM signaling. Overall, functions of individual MAP kinase pathways in pathogenesis and stress responses have been well characterized in a number of fungal pathogens, showing the conserved genetic elements with diverged functions, likely by rewiring transcriptional regulatory networks. In the near future, applications of genomics and proteomics approaches will likely lead to better understanding of crosstalk among the MAPKs and with other signaling pathways as well as roles of MAPKs in defense against other microbes (biotic interactions).

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Cbk1 kinase and Bck2 control MAP kinase activation and inactivation during heat shock

Cited by 21 publications

References 80 publications

The RAM Network in Pathogenic Fungi

The RAM Network in Pathogenic Fungi

A walk-through MAPK structure and functionality with the 30-year-old yeast MAPK Slt2

Regulation of biotic interactions and responses to abiotic stresses by MAP kinase pathways in plant pathogenic fungi

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