PDE4 cAMP-specific phosphodiesterases

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This chapter discusses the cyclic nucleotide phosphodiesterases (PDE4) cyclic Adenosine monophosphate (cAMP)-specific phosphodiesterases. Inhibitors selective for PDE4 enzymes have proved to be extremely informative in identifying the key role that this enzyme activity plays in regulating a variety of important processes related to the inflammatory processes, cell survival, memory, and learning. Molecular biological studies have proved to be crucial in delineating the diversity of this enzyme family. The fact that this diversity has been sustained during evolution, and that particular PDE4 isoenzymes are selectively expressed in different cells, suggests that the various PDE4 isoforms have distinct roles in regulating particular cellular processes. PDE4B, 4C, and 4D isoenzymes are regulated by growth stimulatory responses mediated as a consequence of extracellular-signal-regulated kinases (ERK) activation. In contrast to this, the commonly expressed PDE4A4/5 long form can be regulated through PI-3 kinase-dependent processes and provides a unique target for caspase-3 action, implying a role in cell survival. Indeed, the fact that caspase-3 activation serves to disrupt the intracellular targeting of this enzyme may serve as a paradigm for a means of altering/ablating the role of a PDE4 enzyme, by removing it from a functionally relevant compartment. In this way, new generations of isoenzyme selective inhibitors might be attained.

References (292)

  • M.D Houslay et al.

    Trends Biochem. Sci.

    (1997)
  • J.D Scott

    Pharmacol. Therapeutics

    (1991)
  • S.H Soderling et al.

    Curr. Opin. Cell. Biol.

    (2000)
  • V.C Manganiello et al.

    Arch. Biochem. Biophys.

    (1995)
  • V.C Manganiello et al.

    Cell. Signal.

    (1995)
  • G Bolger

    Cell. Signal.

    (1994)
  • M.D Houslay

    Semin. Cell. Dev. Biol.

    (1998)
  • M.D Houslay et al.

    Adv. Pharmacol.

    (1998)
  • W.J Thompson

    Pharmacol. Therapeutics

    (1991)
  • D.F Rogers et al.

    Trends Pharmacol. Sci.

    (1998)
  • J.E Souness et al.

    Cell. Signal.

    (1997)
  • D Spina et al.

    Adv. Pharmacol.

    (1998)
  • T.P Dousa

    Kidney Int.

    (1999)
  • J.S Hayes et al.

    J. Biol. Chem.

    (1980)
  • I McPhee et al.

    J. Biol. Chem.

    (1999)
  • M Colledge et al.

    Trends Cell Biol.

    (1999)
  • M.C Faux et al.

    Cell (Cambridge, Mass.)

    (1996)
  • T.M Klauck et al.

    Cell. Signal.

    (1995)
  • B.J Murphy et al.

    Trends Cardiovasc. Med.

    (1998)
  • M.D Houslay

    Adv. Enzyme Regulation

    (1995)
  • V.C Manganiello

    J. Mol. Cell. Cardiol.

    (1987)
  • S.H Francis et al.

    J. Biol. Chem.

    (1994)
  • I.V Turko et al.

    J. Biol. Chem.

    (1998)
  • G.A Omburo et al.

    Cell. Signal.

    (1998)
  • G.A Omburo et al.

    Arch. Biochem. Biophys.

    (1995)
  • W Zhang et al.

    Blood

    (2000)
  • C Yan et al.

    J. Biol. Chem.

    (1996)
  • W.K Sonnenburg et al.

    Methods

    (1998)
  • H Mou et al.

    J. Biol. Chem.

    (1999)
  • K Fujishige et al.

    J. Biol. Chem.

    (1999)
  • K Yuasa et al.

    J. Biol. Chem.

    (2000)
  • L Aravind et al.

    Trends Biochem. Sci.

    (1997)
  • J.B Shabb et al.

    J. Biol. Chem.

    (1992)
  • A.E Granovsky et al.

    J. Biol. Chem.

    (1998)
  • J.D Corbin et al.

    J. Biol. Chem.

    (1999)
  • W.K Sonnenburg et al.

    J. Biol. Chem.

    (1991)
  • E Degerman et al.

    J. Biol. Chem.

    (1997)
  • S.J Beebe et al.

    J. Biol. Chem.

    (1985)
  • J.A Smith et al.

    J. Biol. Chem.

    (2000)
  • A Lochhead et al.

    J. Biol. Chem.

    (1997)
  • S Yarfitz et al.

    J. Biol. Chem.

    (1994)
  • L Lagnado et al.

    Neuron

    (1992)
  • N.O Artemyev et al.

    Methods

    (1998)
  • S.H Soderling et al.

    J. Biol. Chem.

    (1998)
  • C.S Rubin

    Biochim. Biophys. Acta

    (1994)
  • M Montminy

    Annu. Rev. Biochem.

    (1997)
  • S.H Francis et al.

    Annu. Rev. Physiol.

    (1994)
  • M.J Smit et al.

    Adv. Second Messenger Phosphoprotein Res.

    (1998)
  • N Defer et al.

    Am. J. Physiol. Renal Physiol.

    (2000)
  • D Juilfs et al.
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