Signalling

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Modelling

Mitochondrial activity signalling: The PKA pathway

  • Cyr1-cAMP-PKA
Paper.svg Tomohiro Yorimitsu, Shadia Zaman, James R. Broach and Daniel J. Klionsky (2002)
Protein kinase A and Sch9 cooperatively regulate induction of autophagy in Saccharomyces cerevisiae
PubMed (title) PubMed (ID) Google Vorlage:Paper
Paper.svg Arti Santhanam, Alan Hartley, Katrin Duvel, James R. Broach and Stephen Garrett (2004)
PP2A Phosphatase Activity Is Required for Stress and Tor Kinase Regulation of Yeast Stress Response Factor Msn2p
PubMed (title) PubMed (ID) Google Vorlage:Paper
  • Msn2 contains several functionally different phosphorylation sites
  • phosphorylation contributes to cytoplasmatic retention of Msn2
  • PKA inactivation leads to Msn2 nuclear localization
  • => under nutrient-rich conditions PKA is active and phosphorylates (inactivates) Msn2 (-> cytoplasmatic localization)

TORC1

Paper.svg Takeshi Noda and Yoshinori Ohsumi (1998)
Tor, a phosphatidylinositol kinase homologue, controls autophagy in yeast
PubMed (title) PubMed (ID) Google Vorlage:Paper
  • ... When rapamycin, an inhibitor of Tor function, is added, autophagy is induced even in cells growing in nutrient-rich medium ...
  • ... a high concentration of cAMP is inhibitory for induction of autophagy ...

Stress and nitrogen starvation signal integration: The Tor-Tap42-PP2A pathway

Paper.svg Arti Santhanam, Alan Hartley, Katrin Duvel, James R. Broach and Stephen Garrett (2004)
PP2A Phosphatase Activity Is Required for Stress and Tor Kinase Regulation of Yeast Stress Response Factor Msn2p
PubMed (title) PubMed (ID) Google Vorlage:Paper
  • Msn2: usually cytoplasmatic, nuclear on stress and nitrogen starvation
  • rapamycin or inactivation of Tap42 cause sustained Msn2 nuclear localization
  • rapamycin affects Msn2 localization via Tap42
  • Tap42 is an inhibitor of PP2A
  • PP2A inhibits nuclear import of Msn2
  • PP2A is required for nuclear localization of Msn2 in response to stress (heat shock, osmotic shock)
  • PP2A is required for nuclear localization of Msn2 in response to nitrogen starvation but not glucose starvation
  • Tip41 plays an active role in transducing the signal between Tap42 and the protein phosphatase complex
Paper.svg Rempola B, Kaniak A, Migdalski A, et al. (2000)
Functional analysis of RRD1 (YIL153w) and RRD2 (YPL152w), which encode two putative activators of the phosphotyrosyl phosphatase activity of PP2A in Saccharomyces cerevisiae
PubMed (title) PubMed (ID) Google Vorlage:Paper

Unspecific starvation signal integration: The signal integrator Rim15

Paper.svg Pedruzzi I, Dubouloz F, Cameroni E, Wanke V, Roosen J, Winderickx J, De Virgilio C (2003)
TOR and PKA signaling pathways converge on the protein kinase Rim15 to control entry into G0
PubMed (title) PubMed (ID) Google Vorlage:Paper
Paper.svg Swinnen et al (2006)
Rim15 and the crossroads of nutrient signalling pathways in Saccharomyces cerevisiae
PubMed (title) PubMed (ID) Google Vorlage:Paper
  • Rim15 was found to integrate signals derived from several different nutrient-sensory kinases (i.e., PKA, TORC1, Sch9, and Pho85-Pho80) that transmit information on the availability of different nutrients
  • Identification of Rim15 as regulator of meiosis: Rim15 was found ... to promote the functional interaction between Ume6 and Ime1 by stimulating the removal of the Rpd3/Sin3 HDAC from the promoters of EMGs in response to depletion of glucose and nitrogen
  • PKA-mediated phosphorylation of Rim15 ... strongly inhibits its kinase activity
  • three transcription factors, Msn2, Msn4, and Gis1, almost entirely account for the Rim15-dependent effects on transcription during glucose limitation
  • mutants lacking Rim15 fail to properly enter G0 following rapamycin treatment
  • TORC1 abolishes the cytoplasmic retention and thereby favours the cytoplasmic-to-nuclear translocation of Rim15
  • Rim15 integrates signals from at least four nutrient-sensitive protein kinases, namely TORC1, Sch9 and Pho85-Pho80, which control sub-cellular localization, and PKA, which controls the activity of Rim15
  • Although direct phosphorylation of the transcription factors by Rim15 is conceivable, Rim15 may alternatively regulate ... interactions between these factors and the general transcription machinery or activate transcription from Msn2/4- and Gis1-dependent promoters through chromatin remodeling

Taken together with the above findings of Rim15 being involved in chromatin remodeling in response to nutrient availability, it seems likely, that Rim15 is not directly interacting with Msn2/4, but rather supports it's activity as transcriptional activator via remodeling of chromatin. Rim15 therefore not only integrates various stress signals of different nature, but also prepares yeast for dramatic changes in gene expression via chromatin remodeling. The fact that delta rim15 mutants fail to enter cell cycle arrest in response to the TORC1 nitrogen starvation pathway, a phenotype that was previously observed in cells lacking Whi2 or Psr respectively, being thus unable to activate Msn2/4, indicates, that Rim15-confered chromatin remodeling is essential for expression of STRE genes via Msn2/4.

sulfur

Fermentable growth medium (FGM) availability signalling: The Sch9 pathway

  • Like TORC1, Sch9 is required for cytoplasmic retention of Rim15 during exponential growth on glucose-containing medium

Phosphate starvation signalling: The PHO pathway

  • Signalling phosphate starvation in yeast is mediated by the PHO pathway, which consists of the cyclin-dependent kinase (CDK) Pho85 and its cyclin partner Pho80, the CDK inhibitor (CKI) Pho81 and the Pho4 transcription factor
  • Rim15 represents a target of the Pho85-Pho80 kinase complex
  • Pho85-Pho80 is localized in the nucleus and TORC1 in the cytoplasm
  • Elevated expression of stress response genes resulting from deletion of PHO85

Carbohydrate sensory?: The Yak1 kinase

Paper.svg Lee et al (2008)
Yeast Yak1 kinase, a bridge between PKA and stress-responsive transcription factors, Hsf1 and Msn2/Msn4
PubMed (title) PubMed (ID) Google Vorlage:Paper
Recent evidence shows that yeast cells also react quickly to a sudden drop in carbohydrate levels.
They respond ... by rapidly reorganizing the intracellular localization of Gal83, a regulatory factor
of the Snf1 kinase, by activation of the Yak1 protein kinase and by changes in the translational
apparatus. They also respond by activating a transcriptional programme dedicated to general stress protection.

Cell wall integrity signalling: The PKC pathway

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Osmosensory signalling: The HOG pathway

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Low pH signalling: The Calcium pathway

Retrograde signalling: Aup1

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