Browsing by Subject "Signal Transduction"

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    Differential functional regulation of protein kinase C (PKC) orthologs in fission yeast.
    (AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 2017-07) Madrid, M.; Vázquez-Marín, B.; Soto, T.; Franco, A.; Gómez-Gil, E.; Vicente-Soler, J.; Gacto, M.; Pérez, P.; Cansado Vizoso, José; Genética y Microbiología
    The two PKC orthologs Pck1 and Pck2 in the fission yeast Schizosaccharomyces pombe operate in a redundant fashion to control essential functions, including morphogenesis and cell wall biosynthesis, as well as the activity of the cell integrity pathway (CIP) and its core element the MAPK Pmk1. We show here that despite the strong structural similarity and functional redundancy of these two enzymes, the mechanisms regulating their maturation, activation, and stabilization have a remarkably distinct biological impact on both kinases. We found that in contrast to Pck2, putative in vivo phosphorylation of Pck1 within the conserved activation loop, turn and hydrophobic motifs is essential for Pck1 stability and biological functions. Constitutive Pck activation promoted dephosphorylation and destabilization of Pck2, while it enhanced Pck1 levels to interfere with proper downstream signaling to the CIP via Pck2. Importantly, whereas catalytic activity was essential for Pck1 function, Pck2 remained partially functional independently of its catalytic activity. Our findings suggest that early divergence from a common ancestor in fission yeast involved important changes in the mechanisms regulating catalytic activation and stability of PKC family members to allow for flexible and dynamic control of downstream functions, including MAPK signaling.