ArticleMolecular and cellular biology2003
Combination of two activating mutations in one HOG1 gene forms hyperactive enzymes that induce growth arrest.
Article in Molecular and cellular biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 57 citations in OpenAlex.
- Cytoplasmic sequestering of a fungal stress-activated MAPK in response to a host plant phenolic acid.PLoS pathogens · 2025Article
- The roles of inducible chromatin and transcriptional memory in cellular defense system responses to redox-active pollutants.Free radical biology & medicine · 2021Review
- Active p38α causes macrovesicular fatty liver in mice.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Hog1-induced transcription of RTC3 and HSP12 is robust and occurs in cells lacking Msn2, Msn4, Hot1 and Sko1.PloS one · 2020Article
- A transcriptome-wide analysis deciphers distinct roles of G1 cyclins in temporal organization of the yeast cell cycle.Scientific reports · 2019Article
- Non-canonical Activities of Hog1 Control Sensitivity ofFrontiers in cellular and infection microbiology · 2018Article
- Mutational Analysis of a Conserved Glutamate Reveals Unique Mechanistic and Structural Features of the Phosphatase PRL-3.ACS omega · 2017Article
- Variants of the yeast MAPK Mpk1 are fully functional independently of activation loop phosphorylation.Molecular biology of the cell · 2016Article
- Tighter αC-helix-αL16-helix interactions seem to make p38α less prone to activation by autophosphorylation than Hog1.Bioscience reports · 2016Article
- The yeast Hot1 transcription factor is critical for activating a single target gene, STL1.Molecular biology of the cell · 2015Article
- Activation of stress signalling pathways enhances tolerance of fungi to chemical fungicides and antifungal proteins.Cellular and molecular life sciences : CMLS · 2014Review
- An integrated pathway system modeling of Saccharomyces cerevisiae HOG pathway: a Petri net based approach.Molecular biology reports · 2013Article
- Response to hyperosmotic stress.Genetics · 2012Review
- Osmostress induces autophosphorylation of Hog1 via a C-terminal regulatory region that is conserved in p38α.PloS one · 2012Article
- Controlling gene expression in response to stress.Nature reviews. Genetics · 2011Review
- The stress-activated protein kinase Hog1 mediates S phase delay in response to osmostress.Molecular biology of the cell · 2009Article
- Loss of cardiolipin leads to longevity defects that are alleviated by alterations in stress response signaling.The Journal of biological chemistry · 2009Article
- Two-component response regulators Ssk1p and Skn7p additively regulate high-osmolarity adaptation and fungicide sensitivity in Cochliobolus heterostrophus.Eukaryotic cell · 2007Article
- Expressed in the yeast Saccharomyces cerevisiae, human ERK5 is a client of the Hsp90 chaperone that complements loss of the Slt2p (Mpk1p) cell integrity stress-activated protein kinase.Eukaryotic cell · 2006Article
- Phosphorylation of Hsl1 by Hog1 leads to a G2 arrest essential for cell survival at high osmolarity.The EMBO journal · 2006Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitogen-activated protein kinases (MAPKs) play key roles in differentiation, growth, proliferation, and apoptosis. Although MAPKs have been extensively studied, the precise function, specific substrates, and target genes of each MAPK are not known. These issues could be addressed by sole activation of a given MAPK, e.g., through the use of constitutively active MAPK enzymes. We have recently reported the isolation of eight hyperactive mutants of the Saccharomyces cerevisiae MAPK Hog1, each of which bears a distinct single point mutation. These mutants acquired high intrinsic catalytic activity but did not impose the full biological potential of the Hog1 pathway. Here we describe our attempt to obtain a MAPK that is more active than the previous mutants both catalytically and biologically. We combined two different activating point mutations in the same gene and found that two of the resulting double mutants acquired unusual properties. These alleles, HOG1(D170A,F318L) and HOG1(D170A,F318S), induced a severe growth inhibition and had to be studied through an inducible expression system. This growth inhibition correlated with very high spontaneous (in the absence of any stimulation) catalytic activity and strong induction of Hog1 target genes. Furthermore, analysis of the phosphorylation status of these active alleles shows that their acquired intrinsic activity is independent of either phospho-Thr174 or phospho-Tyr176. Through fluorescence-activated cell sorting analysis, we show that the effect on cell growth inhibition is not a result of cell death. This study provides the first example of a MAPK that is intrinsically activated by mutations and induces a strong biological effect.
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