PI SIGNALLING · Phosphate sensing for activation of the protein kinase A pathway in yeast
6РП — Действия „Мария Кюри“
- Период
- 2004-11-01 → 2006-10-31
- Финансиране от ЕС
- 142 887 €
- Участници
- 1
- Схема
- IIF
Линиите свързват координатора с партньорите.
Накратко на български
Протеинът Pho84 при дрождите действа като сензор, който засича фосфати и активира клетъчни сигнали, без задължително да транспортира тези вещества. Това помага да се разбере как транспортните протеини в еукариотните клетки могат да функционират като рецептори за хранителни вещества.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Final Activity Report Summary - PI SIGNALLING (Phosphate sensing for activation of the protein kinase A pathway in yeast)
Specific nutrient transporters in eukaryotic cells have recently been suggested to function as nutrient receptors for activation of signalling pathways. In the yeast Saccharomyces cerevisiae, the Pho84 phosphate transporter appears to mediate phosphate-induced activation of the PKA pathway in phosphate-starved cells. We showed that addition of phosphate-containing compounds such as glycerol-3-phosphate (Gly3P) or glycerophosphoinositol (GlyPIno) to phosphate-starved cells triggers rapid activation of trehalase, a well-known protein kinase A (PKA) target. The activation is reduced in mutants with reduced PKA activity and is independent of secreted phosphatase activity. Pho84 is required as for Gly3P- and also for GlypIno-induced trehalase activation but is unable to transport these compounds. The known transporter of GlyPIno is encoded by GIT1 gene. First we discovered that Gly3P is transported inside the cell by Pho91, which is more known as a weak low-affinity phosphate transporter, and Git1 permease. We also showed that the lethality of a yeast phosphate carrier null strain can be rescued by addition of Gly3P as a Pi source and that the Gly3P is taken up in this case by the Git1 carrier. However, deletion of Git1 does not prevent Gly3P-induced trehalase activation nor is Git1 able to support the activation of trehalase. The same is true for the phosphate carriers Pho87, Pho90 and Pho91.Competitive inhibition of phosphate transport by Gly3P or GlyPIno confirms interaction of Gly3P and GlyPIno with the phosphate-binding site of Pho84. These results support the role of Pho84 as a phosphate sensor. We have found the first non-transported agonists of the signalling function of a transporter-receptor identified in eukaryotic cells.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
A central problem in modern cell biology is to elucidate how the cell perceives signals from the surrounding environment and how the signals are transmitted to affect metabolic pathways and gene expression. Increasing evidence indicates that eukaryotic cells also have many specific sensing mechanisms for extra-cellular nutrients, but a major challenge is to distinguish between true signalling and effects due to metabolism. The yeast Saccharomyces cerevisiae is one of the best model systems for eukaryotic cell re search because of its genetic tractability and powerful genomic approaches. Its protein kinase A pathway plays a major role in cellularregulation but its control by specific nutrients is not well understood.The plasma membrane phosphate carriers Pho84 and P ho87 appear to act as phosphate sensors controlling this pathway. The first objective of this proposal is to identify the domains of these proteins involved in phosphate sensing through construction of chimeric proteins with non-sensing carriers. The second objective is to identify downstream factors of the regulatory cascade.This will be done by transposon mutagenesis and multicopy-suppressor isolation in a strain expressing recently isolated constitutively activating ale of Pho84 causing reduced viability under stress conditions. Recent work has also indicated possible involvement of Pho85, a central cyclin-dependent protein kinase in phosphate regulatory pathways. Hence, the effect of Pho85 deletion on phosphate control of protein kinase A targets will also be determined.Pho85 is a homologue of human Cdk5 kinase, which has been implicated in several metabolic and developmental processes, as well as in neuro degenerative and other diseases. Since the function of cyclin-dependent protein kinases is conserved in evolution, the role ofPho85 in co-ordination of phosphate and PKA signalling in yeast might reveal important novel features.
Оригинален текст от CORDIS (на английски).
Участници
- FLANDERS INTERUNIVERSITY INSTITUTE FOR BIOTECHNOLOGY VZW · ZWIJNAARDEКоординаторБелгия
Връзки
Данни: CORDIS, © Европейски съюз