Cyclic AMP-specific PDE4 Phosphodiesterases as Critical Components of Cyclic AMP Signaling

Marco Conti,Wito Richter,Celine Mehats,Gabriel Livera,Jy-Young Park,Catherine Jin

doi:10.1074/jbc.r200029200

Abstract

Cyclic AMP-specific PDE4 Phosphodiesterases as Critical Components of Cyclic AMP Signaling

Highlights

Ture, there are 4 or 5 transcripts for PDE4A, 4 for PDE4B, possibly 3 for PDE4C, and 5 or more for PDE4D, for a total of at least 16 open reading frames in humans
Together with the finding that an antibody that binds UCR2 induces an increase in Vmax [13], these properties of the long forms have led to a model whereby UCR1 phosphorylation modulates the interactions of UCR2 with the catalytic domain, altering its conformation and activity
It is well established that a subgroup of PDE4 inhibitors, the prototype being rolipram, bind to the enzyme with kinetics that indicates the presence of multiple conformational states [16]

Summary

Introduction

Ture, there are 4 or 5 transcripts for PDE4A, 4 for PDE4B, possibly 3 for PDE4C, and 5 or more for PDE4D, for a total of at least 16 open reading frames in humans. Together with the finding that an antibody that binds UCR2 induces an increase in Vmax [13], these properties of the long forms have led to a model whereby UCR1 phosphorylation modulates the interactions of UCR2 with the catalytic domain, altering its conformation and activity. Minireview: PDE4s and cAMP Signaling though it was initially thought that this anomalous behavior is due to the presence of an allosteric site, it is accepted that rolipram binds to two or more conformers of the catalytic domain.

Results

Conclusion