Mathematical modeling reveals differential regulation of MAPK activity by phosphatase proteins in the yeast pheromone response pathway

2017 ◽  
Vol 13 (7) ◽  
pp. 1323-1335 ◽  
Author(s):  
Nathan Dyjack ◽  
Cassandra Azeredo-Tseng ◽  
Necmettin Yildirim
Keyword(s):  
Mathematical Modeling ◽  
Cellular Responses ◽  
Differential Regulation ◽  
Pheromone Response ◽  
Pheromone Response Pathway ◽  
Mapk Activity ◽  
Adaptation Mechanisms ◽  
External Signals

To prevent indefinite cellular responses to external signals, cells utilize various adaptation mechanisms.

scholarly journals Signalling in the Yeasts: An Informational Cascade with Links to the Filamentous Fungi

1998 ◽  
Vol 62 (2) ◽  
pp. 249-274 ◽  
Author(s):  
Flora Banuett
Keyword(s):  
Filamentous Fungi ◽  
Mammalian Cells ◽  
Mapk Cascade ◽  
Mitogen Activated Protein Kinase ◽  
Signalling Pathways ◽  
Pheromone Response ◽  
Protein Activity ◽  
Pheromone Response Pathway ◽  
Mapk Cascades ◽  
External Signals

SUMMARY All cells, from bacteria and yeasts to mammalian cells, respond to cues from their environment. A variety of mechanisms exist for the transduction of these external signals to the interior of the cell, resulting in altered patterns of protein activity. Eukaryotic cells commonly transduce external cues via a conserved module composed of three protein kinases, the mitogen-activated protein kinase (MAPK) cascade. This module can then activate substrates, some of which include transcriptional activators. Multiple MAPK signalling pathways coexist in a cell. This review considers different MAPK cascade signalling pathways that govern several aspects of the life cycle of budding and fission yeasts: conjugation and meiosis by the pheromone response pathway, stress response by the high-osmolarity sensing pathway, cell wall biosynthesis in response to activation of the low-osmolarity and heat-sensing pathway, and pseudohyphal growth in response to activation of a subset of the components of the pheromone response pathway. Because the MAPK cascade components are highly conserved, a key question in studies of these pathways is the mechanism by which specificity of response is achieved. Several other issues to be addressed in this review concern the nature of the receptors used to sense the external signals and the mechanism by which the receptors communicate with other components leading to activation of the MAPK cascade. Recently, it has become apparent that MAPK cascades are important in governing the pathogenicity of filamentous fungi.

scholarly journals Signal-mediated localization of Candida albicans pheromone response pathway components

2020 ◽  
Author(s):  
Anna Carolina Borges Pereira Costa ◽  
Raha Parvizi Omran ◽  
Chris Law ◽  
Vanessa Dumeaux ◽  
Malcolm Whiteway
Keyword(s):  
Candida Albicans ◽  
Map Kinase ◽  
Nuclear Localization ◽  
Map Kinases ◽  
Critical Role ◽  
Cell Periphery ◽  
Pheromone Response ◽  
Pheromone Response Pathway ◽  
Localization Signal ◽  
In Cells

Abstract Candida albicans opaque cells release pheromones to stimulate cells of opposite mating type to activate their pheromone response pathway. Although this fungal pathogen shares orthologous proteins involved in the process with Saccharomyces cerevisiae, the pathway in each organism has unique characteristics. We have used GFP-tagged fusion proteins to investigate the localization of the scaffold protein Cst5, as well as the MAP kinases Cek1 and Cek2, during pheromone response in C. albicans. In wild-type cells, pheromone treatment directed Cst5-GFP to surface puncta concentrated at the tips of mating projections. These puncta failed to form in cells defective in either the Gα or β subunits. However, they still formed in response to pheromone in cells missing Ste11, but with the puncta distributed around the cell periphery in the absence of mating projections. These puncta were absent from hst7Δ/Δ cells, but could be detected in the ste11Δ/Δ hst7Δ/Δ double mutant. Cek2-GFP showed a strong nuclear localization late in the response, consistent with a role in adaptation, while Cek1-GFP showed a weaker, but early increase in nuclear localization after pheromone treatment. Activation loop phosphorylation of both Cek1 and Cek2 required the presence of Ste11. In contrast to Cek2-GFP, which showed no localization signal in ste11Δ/Δ cells, Cek1-GFP showed enhanced nuclear localization that was pheromone independent in the ste11Δ/Δ mutant. The results are consistent with CaSte11 facilitating Hst7-mediated MAP kinase phosphorylation and also playing a potentially critical role in both MAP kinase and Cst5 scaffold localization.

A yeast mitogen-activated protein kinase homolog (Mpk1p) mediates signalling by protein kinase C

1993 ◽  
Vol 13 (5) ◽  
pp. 3067-3075 ◽  
Author(s):  
K S Lee ◽  
K Irie ◽  
Y Gotoh ◽  
Y Watanabe ◽  
H Araki ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Map Kinase ◽  
Protein Kinases ◽  
Map Kinases ◽  
Pheromone Response ◽  
Pheromone Response Pathway ◽  
Kinase C ◽  
Mitogen Activated Protein ◽  
Kinase Cascade ◽  
Protein Kinase Cascade

Mitogen-activated protein (MAP) kinases are activated in response to a variety of stimuli through a protein kinase cascade that results in their phosphorylation on tyrosine and threonine residues. The molecular nature of this cascade is just beginning to emerge. Here we report the isolation of a Saccharomyces cerevisiae gene encoding a functional analog of mammalian MAP kinases, designated MPK1 (for MAP kinase). The MPK1 gene was isolated as a dosage-dependent suppressor of the cell lysis defect associated with deletion of the BCK1 gene. The BCK1 gene is also predicted to encode a protein kinase which has been proposed to function downstream of the protein kinase C isozyme encoded by PKC1. The MPK1 gene possesses a 1.5-kb uninterrupted open reading frame predicted to encode a 53-kDa protein. The predicted Mpk1 protein (Mpk1p) shares 48 to 50% sequence identity with Xenopus MAP kinase and with the yeast mating pheromone response pathway components, Fus3p and Kss1p. Deletion of MPK1 resulted in a temperature-dependent cell lysis defect that was virtually indistinguishable from that resulting from deletion of BCK1, suggesting that the protein kinases encoded by these genes function in a common pathway. Expression of Xenopus MAP kinase suppressed the defect associated with loss of MPK1 but not the mating-related defects associated with loss of FUS3 or KSS1, indicating functional conservation between the former two protein kinases. Mutation of the presumptive phosphorylated tyrosine and threonine residues of Mpk1p individually to phenylalanine and alanine, respectively, severely impaired Mpk1p function. Additional epistasis experiments, and the overall architectural similarity between the PKC1-mediated pathway and the pheromone response pathway, suggest that Pkc1p regulates a protein kinase cascade in which Bck1p activates a pair of protein kinases, designated Mkk1p and Mkk2p (for MAP kinase-kinase), which in turn activate Mpk1p.

Functional domains of the yeast STE12 protein, a pheromone-responsive transcriptional activator

1993 ◽  
Vol 13 (6) ◽  
pp. 3765-3772
Author(s):  
C Kirkman-Correia ◽  
I L Stroke ◽  
S Fields
Keyword(s):  
Transcriptional Activity ◽  
Protein A ◽  
Pheromone Response ◽  
Yeast Saccharomyces Cerevisiae ◽  
Mutant Proteins ◽  
Pheromone Response Pathway ◽  
Cell Type Specific ◽  
Carboxy Terminal ◽  
Induced Signal ◽  
Insertion Mutants

The pheromone response pathway of the yeast Saccharomyces cerevisiae is necessary for the basal level of transcription of cell-type-specific genes, as well as the induced level observed after pheromone treatment. The STE12 protein binds to the DNA sequence designated the pheromone response element and is a target of the pheromone-induced signal. We generated 6-nucleotide linker insertion mutants, internal-deletion mutants, and carboxy-terminal truncation mutants of STE12 and assayed them for their ability to restore mating and transcriptional activity to a ste12 delta strain. Two of these mutant proteins retain the capacity to mediate basal transcription but show little or no induced transcription upon pheromone treatment. Cells producing these proteins cannot mate, formally demonstrating that the ability to respond to pheromone by increasing gene expression is essential for the mating process. Since distinct domains of STE12 appear to be required for basal versus induced transcription, we suggest that the pheromone-induced signal is likely to target residues of the protein different from those targeted by the basal signal because of the constitutive activity of the response pathway. Our analysis of mutant STE12 proteins also indicates that only the DNA-binding domain is sensitive to the small changes caused by the linker insertions. In addition, we show that, while the carboxy-terminal sequences necessary for STE12 to form a complex with the transcription factor MCM1 are not essential for mating, these sequences are required for optimal transcriptional activity.

scholarly journals Prey sensing and response in a nematode-trapping fungus is governed by the MAPK pheromone response pathway

Genetics ◽  
2020 ◽  
Vol 217 (2) ◽  
Author(s):  
Sheng-An Chen ◽  
Hung-Che Lin ◽  
Frank C Schroeder ◽  
Yen-Ping Hsueh
Keyword(s):  
Mapk Pathway ◽  
Transcriptional Profiling ◽  
Vital Role ◽  
Molecular Signature ◽  
Food Sources ◽  
Small Subset ◽  
Interspecies Interactions ◽  
Pheromone Response ◽  
Pheromone Response Pathway ◽  
Pheromone Signaling

Abstract Detection of surrounding organisms in the environment plays a major role in the evolution of interspecies interactions, such as predator–prey relationships. Nematode-trapping fungi (NTF) are predators that develop specialized trap structures to capture, kill, and consume nematodes when food sources are limited. Despite the identification of various factors that induce trap morphogenesis, the mechanisms underlying the differentiation process have remained largely unclear. Here, we demonstrate that the highly conserved pheromone-response MAPK pathway is essential for sensing ascarosides, a conserved molecular signature of nemaotdes, and is required for the predatory lifestyle switch in the NTF Arthrobotrys oligospora. Gene deletion of STE7 (MAPKK) and FUS3 (MAPK) abolished nematode-induced trap morphogenesis and conidiation and impaired the growth of hyphae. The conserved transcription factor Ste12 acting downstream of the pheromone-response pathway also plays a vital role in the predation of A. oligospora. Transcriptional profiling of a ste12 mutant identified a small subset of genes with diverse functions that are Ste12 dependent and could trigger trap differentiation. Our work has revealed that A. oligospora perceives and interprets the ascarosides produced by nematodes via the conserved pheromone signaling pathway in fungi, providing molecular insights into the mechanisms of communication between a fungal predator and its nematode prey.

scholarly journals Ca+2 Signal is Generated Only Once in the Mating Pheromone Response Pathway in Saccharomyces cerevisiae.

2000 ◽  
Vol 25 (2) ◽  
pp. 125-131 ◽  
Author(s):  
Junko Nakajima-Shimada ◽  
Shuichi Sakaguchi ◽  
Frederick I. Tsuji ◽  
Yasuhiro Anraku ◽  
Hidetoshi Iida
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Pheromone Response ◽  
Mating Pheromone ◽  
Pheromone Response Pathway

scholarly journals The pheromone response pathway ofKluyveromyces lactis

2006 ◽  
Vol 6 (3) ◽  
pp. 336-344 ◽  
Author(s):  
Roberto Coria ◽  
Laura Kawasaki ◽  
Francisco Torres-Quiroz ◽  
Laura Ongay-Larios ◽  
Edith Sánchez-Paredes ◽  
...  
Keyword(s):  
Pheromone Response ◽  
Pheromone Response Pathway

scholarly journals Regulation of the yeast pheromone response pathway by G protein subunits.

1990 ◽  
Vol 9 (3) ◽  
pp. 691-696 ◽  
Author(s):  
S. Nomoto ◽  
N. Nakayama ◽  
K. Arai ◽  
K. Matsumoto
Keyword(s):  
G Protein ◽  
Pheromone Response ◽  
Protein Subunits ◽  
Pheromone Response Pathway
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