Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.24 (mitogen-activated protein kinase)
 95,810 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mitogen-activated protein (MAP) kinases comprise a family of conserved, eukaryotic enzymes that mediate responses to a wide variety of extracellular stimuli. In yeast, different signal transduction pathways utilize distinct MAP kinase family members. We have identified a new yeast MAP kinase gene (named SMK1) that is required for the completion of sporulation. Molecular and cytologic markers indicate that meiotic development proceeds normally in homozygous smk1-delta 1 diploids through meiosis II. However, light and electron microscopy show that smk1 asci are defective in organizing spore wall assembly. Consistent with a defect in spore wall assembly, smk1-delta 1 mutant asci display enhanced sensitivities to enzymatic digestion, heat shock, and exposure to ether. SMK1 mRNA, which is not detectable in vegetative cells, is derepressed at least 200-fold just prior to prospore enclosure. We propose that the SMK1 MAP kinase participates in a developmentally regulated signal transduction pathway that coordinates cytodifferentiation events with the transcriptional program.
 ...
PMID:SMK1, a developmentally regulated MAP kinase, is required for spore wall assembly in Saccharomyces cerevisiae. 795 85

Mitogen-activated protein (MAP) kinase pathways are evolutionarily conserved kinase cascades that are required for the response of eukaryotic cells to a wide variety of environmental stimuli. MAP kinase pathways are also required for the execution of developmental and differentiative programs in a variety of cell and tissue types. SMK1 encodes a developmentally regulated MAP kinase in yeast that is required for spore wall morphogenesis. Cyclin-dependent kinase-activating kinases (CAKs) phosphorylate a conserved threonine residue in the activating loop of cyclin-dependent kinases. CAK1 encodes the major CAK activity in yeast and is required for cell cycle progression. The work presented here demonstrates that CAK1 functions positively in the spore wall morphogenesis pathway. First, CAK1 has been isolated as a dosage suppressor of a conditional smk1 mutant that is defective for spore wall morphogenesis. Second, CAK1 mRNA accumulates during spore development contemporaneously with SMK1 mRNA. Third, cak1 mutant strains have been isolated that are able to complete meiosis I and II but are specifically defective in assembly of the spore wall. These results show that cell cycle progression and morphogenetic pathways can be regulated by a single gene product and suggest mechanisms for coordinating these processes during development.
 ...
PMID:The CDK-activating kinase CAK1 can dosage suppress sporulation defects of smk1 MAP kinase mutants and is required for spore wall morphogenesis in Saccharomyces cerevisiae. 913 46

The SMK1 mitogen-activated protein kinase is required for spore morphogenesis in Saccharomyces cerevisiae. In contrast to the multiple aberrant spore wall assembly patterns seen even within a single smk1 null ascus, different smk1 missense mutants block in a coordinated fashion at intermediate stages. One smk1 mutant forms asci in which the four spores are surrounded only by prospore wall-like structures, while another smk1 mutant forms asci in which the spores are surrounded by inner but not outer spore wall layers. Stepwise increases in gene dosage of a hypomorphic smk1 allele allow for the completion of progressively later morphological and biochemical events and for the acquisition of distinct spore-resistance phenotypes. Furthermore, smk1 allelic spore phenotypes can be recapitulated by reducing wild-type SMK1 expression. The data demonstrate that SMK1 is required for the execution of multiple steps in spore morphogenesis that require increasing thresholds of SMK1 activity. These results suggest that quantitative changes in mitogen-activated protein kinase signaling play a role in coordinating multiple events of a single cellular differentiation program.
 ...
PMID:Distinct steps in yeast spore morphogenesis require distinct SMK1 MAP kinase thresholds. 1010 Nov 60

Sclerotial development is fundamental to the disease cycle of the omnivorous broad host range fungal phytopathogen Sclerotinia sclerotiorum. We have isolated a highly conserved homolog of ERK-type mitogen-activated protein kinases (MAPKs) from S. sclerotiorum (Smk1) and have demonstrated that Smk1 is required for sclerotial development. The smk1 transcription and MAPK enzyme activity are induced dramatically during sclerotiogenesis, especially during the production of sclerotial initials. When PD98059 (a specific inhibitor of the activation of MAPK by MAPK kinase) was applied to differentiating cultures or when antisense expression of smk1 was induced, sclerotial maturation was impaired. The smk1 transcript levels were highest under acidic pH conditions, suggesting that Smk1 regulates sclerotial development via a pH-dependent signaling pathway, involving the accumulation of oxalic acid, a previously identified pathogenicity factor that functions at least in part by reducing pH. Addition of cyclic AMP (cAMP) inhibited smk1 transcription, MAPK activation, and sclerotial development. Thus, S. sclerotiorum can coordinate environmental signals (such as pH) to trigger a signaling pathway mediated by Smk1 to induce sclerotia formation, and this pathway is negatively regulated by cAMP.
 ...
PMID:MAPK regulation of sclerotial development in Sclerotinia sclerotiorum is linked with pH and cAMP sensing. 1507 73

Rsc1 and Rsc2 are alternative bromodomain-containing subunits of the ATP-dependent RSC chromatin remodeling complex in Saccharomyces cerevisiae. Smk1 is a sporulation-specific mitogen-activated protein kinase homolog that is required for the postmeiotic events of spore formation. In this study we show that RSC1 and RSC2 are haploinsufficient for spore formation in a smk1 hypomorph. Moreover, diploids lacking Rsc1 or Rsc2 show a subset of smk1-like phenotypes. High-copy-number RSC1 plasmids do not suppress rsc2-Delta/rsc2-Delta sporulation defects, and high-copy-number RSC2 plasmids do not suppress rsc1-Delta/rsc1-Delta sporulation defects. Mid-late sporulation-specific genes, which are normally expressed while key steps in spore assembly occur and which include genes that are required for spore wall formation, are not expressed in cells lacking Rsc1 or Rsc2. We speculate that the combined action of Rsc1 and Rsc2 at mid-late promoters is specifically required for the proper expression of this uniquely timed set of genes. Our data suggest that Smk1 and Rsc1/2 define parallel pathways that converge to provide signaling information and the expression of gene products, respectively, that are required for spore morphogenesis.
 ...
PMID:RSC1 and RSC2 are required for expression of mid-late sporulation-specific genes in Saccharomyces cerevisiae. 1530 24

ABSTRACT Sclerotia of Sclerotinia sclerotiorum are pigmented, multihyphal structures that play a central role in the life and infection cycles of this pathogen. Sclerotial formation has been shown to be affected by increased intracellular cAMP levels. Cyclic AMP (cAMP) is a key modulator of cAMP-dependent protein kinase A (PKA) and the latter may prove to play a significant role in sclerotial development. Therefore, we monitored changes in relative PKA activity levels during sclerotial development. To do so, we first developed conditions for near-synchronous sclerotial development in culture, based on hyphal maceration and filtering. Relative PKA activity levels increased during the white-sclerotium stage in the wild-type strain, while low levels were maintained in nonsclerotium-producing mutants. Furthermore, applying caffeine, an inducer of PKA activity, resulted in increased relative PKA activity levels and was correlated with the formation of sclerotial initial-like aggregates in cultures of the non-sclerotium-producing mutants. In addition, low PKA activities were found in an antisense smk1 strain, which exhibits low extracellular-signal-regulated kinase (ERK)-type mitogen-activated protein kinase (MAPK) activity, and does not produce sclerotia. The changes in PKA activity, as well as the abundance of phosphorylated MAPKs (ERK-like as well as p38-like) that accompany sclerotial development in a distinct developmental phase manner represent a potential target for antifungal intervention.
 ...
PMID:Changes in Protein Kinase A Activity Accompany Sclerotial Development in Sclerotinia sclerotiorum. 1894 42

Meiotic development (sporulation) in the yeast Saccharomyces cerevisiae is induced by nutritional deprivation. Smk1 is a meiosis-specific MAP kinase homolog that controls spore morphogenesis after the meiotic divisions have taken place. In this study, recessive mutants that suppress the sporulation defect of a smk1-2 temperature-sensitive hypomorph were isolated. The suppressors are partial function alleles of CDC25 and CYR1, which encode the Ras GDP/GTP exchange factor and adenyl cyclase, respectively, and MDS3, which encodes a kelch-domain protein previously implicated in Ras/cAMP signaling. Deletion of PMD1, which encodes a Mds3 paralog, also suppressed the smk1-2 phenotype, and a mds3-Delta pmd1-Delta double mutant was a more potent suppressor than either single mutant. The mds3-Delta, pmd1-Delta, and mds3-Delta pmd1-Delta mutants also exhibited mitotic Ras/cAMP phenotypes in the same rank order. The effect of Ras/cAMP pathway mutations on the smk1-2 phenotype required the presence of low levels of glucose. Ime2 is a meiosis-specific CDK-like kinase that is inhibited by low levels of glucose via its carboxy-terminal regulatory domain. IME2-DeltaC241, which removes the carboxy-terminal domain of Ime2, exacerbated the smk1-2 spore formation phenotype and prevented cyr1 mutations from suppressing smk1-2. Inhibition of Ime2 in meiotic cells shortly after Smk1 is expressed revealed that Ime2 promotes phosphorylation of Smk1's activation loop. These findings demonstrate that nutrients can negatively regulate Smk1 through the Ras/cAMP pathway and that Ime2 is a key activator of Smk1 signaling.
 ...
PMID:The Ras/cAMP pathway and the CDK-like kinase Ime2 regulate the MAPK Smk1 and spore morphogenesis in Saccharomyces cerevisiae. 1908 57