Mutations in the Phosphatase Domain of the 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase Result in the Transcriptional Activation of the Alternative Oxidase and Gluconeogenic Pathways in Podospora anserina.

08:00 EDT 10th April 2019 | BioPortfolio

Summary of "Mutations in the Phosphatase Domain of the 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase Result in the Transcriptional Activation of the Alternative Oxidase and Gluconeogenic Pathways in Podospora anserina."

By screening suppressors of a respiratory mutant lacking a functional cytochrome pathway in the filamentous fungus Podospora anserina, we isolated a mutation located in the phosphatase domain of the bi-functional enzyme 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase (PFK-2/FBPase-2). We show that the inactivation of the phosphatase but not of the kinase domain is responsible for the suppressor effect that results from the activation of the RSEs transcription factors that control expression of AOX, an alternative oxidase able to bypass the mitochondria cytochrome pathway of respiration. Remarkably, activation of the RSEs also stimulates the expression of the gluconeogenic enzymes, fructose-1,6 bi-phosphatase (FBPase-1) and phosphoenolpyruvate carboxykinase (PCK-1). We thus reveal in P. anserina an apparently paradoxical situation where the inactivation of the phosphatase domain of PFK-2/FBPase-2, supposed to stimulate glycolysis, is correlated with the transcriptional induction of the gluconeogenic enzymes. Phylogenic analysis revealed the presence of multiple presumed PFK-2/FBPase-2 isoforms in all the species of tested Ascomycetes.


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This article was published in the following journal.

Name: Fungal genetics and biology : FG & B
ISSN: 1096-0937


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Medical and Biotech [MESH] Definitions

An enzyme that catalyzes the conversion of D-fructose 1,6-bisphosphate and water to D-fructose 6-phosphate and orthophosphate. EC

One of four major classes of mammalian serine/threonine specific protein phosphatases. Protein phosphatase 2C is a monomeric enzyme about 42 kDa in size. It shows broad substrate specificity dependent on divalent cations (mainly manganese and magnesium). Three isozymes are known in mammals: PP2C -alpha, -beta and -gamma. In yeast, there are four PP2C homologues: phosphatase PTC1 that have weak tyrosine phosphatase activity, phosphatase PTC2, phosphatase PTC3, and PTC4. Isozymes of PP2C also occur in Arabidopsis thaliana where the kinase-associated protein phosphatase (KAPP) containing a C-terminal PP2C domain, dephosphorylates Ser/Thr receptor-like kinase RLK5.

An allosteric enzyme that regulates glycolysis and gluconeogenesis by catalyzing the transfer of a phosphate group from ATP to fructose-6-phosphate to yield fructose-2,6-bisphosphate, an allosteric effector for the other 6-phosphofructokinase, PHOSPHOFRUCTOKINASE-1. Phosphofructokinase-2 is bifunctional: the dephosphorylated form is a kinase and the phosphorylated form is a phosphatase that breaks down fructose-2,6-bisphosphate to yield fructose-6-phosphate.

An eph family receptor found primarily in BRAIN and THYMUS. The EphB6 receptor is unusual in that its tyrosine kinase domain shares little homology with other members of this class. The unusual tyrosine kinase domain of this receptor appears to result in its lack of tyrosine kinase activity.

A subtype of non-receptor protein tyrosine phosphatases that is characterized by the presence of an amino-terminal FERM domain, an intervening region containing one or more PDZ domains, and a carboxyl-terminal phosphatase domain. Expression of this phosphatase subtype has been observed in BONE MARROW; fetal LIVER; LYMPH NODES; and T LYMPHOCYTES.

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