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Characterization of Ypk1 and Fpk1 downstream targets in TORC2 signalling pathway

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Defense Thèse de doctorat : Univ. Genève, 2018 - Sc. 5182 - 2018/02/23
Abstract Protein phosphorylation performed by protein kinases is a general molecular language that takes a large part in cell signalisation to quickly integrate cues. TOR (Target of Rapamycin) is a widely conserved serine/threonine protein kinase that senses and coordinates diverse stresses. In Saccharomyces cerevisae, TOR can form two complexes TORC1 and TORC2, where only TORC1 is inhibited by Rapamycin. Thus, our knowledge regarding TORC2 downstream pathway remains limited. To overcome this limitation, yeast strains were engineered with which we specially inhibit TORC2 using ATP-competitive inhibitors. Upon increase of plasma membrane tension, TORC2 promotes endocytosis and actin polarization by phosphorylating Ypk1 kinase, which in turn phosphorylates and inhibits Fpk1 kinase. In addition, Fpk1 also phosphorylates Ypk1 N-terminal region. In this thesis, we showed that cross-phosphorylations between Ypk1 and Fpk1 are inhibitory suggesting that this signaling node functions as a rheostat. We also found that phosphorylations in Ypk1 N-terminal region modulate the affinity and the specificity for its substrates. Finally, we found novel effectors, downstream of TORC2 proving that Fpk1 independently regulates actin polarization via flippases and endocytosis via Akl1 kinase.
Keywords Target of Rapamycin Complex 2 (TORC2)EndocytosisActin polarizationFpk1Kinase activity
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URN: urn:nbn:ch:unige-1032418
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Research group Groupe Loewith
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BOURGOINT, Clelia. Characterization of Ypk1 and Fpk1 downstream targets in TORC2 signalling pathway. Université de Genève. Thèse, 2018. https://archive-ouverte.unige.ch/unige:103241

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Deposited on : 2018-03-28

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