Premium
Integrating cAMP and phospholipid signaling: role of phosphodiesterase 3B
Author(s) -
Wilson Lindsay S,
Maurice Donald H
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a796
Subject(s) - second messenger system , phosphodiesterase , adenylyl cyclase , microbiology and biotechnology , phosphodiesterase 3 , effector , pde10a , extracellular , subcellular localization , intracellular , cyclic adenosine monophosphate , signal transduction , biology , context (archaeology) , cell signaling , cyclic nucleotide phosphodiesterase , biochemistry , enzyme , receptor , cytoplasm , paleontology
Cyclic AMP (cAMP) is a ubiquitous intracellular messenger that acts to integrate and translate the information encoded by extracellular messenger molecules, including hormones and neurotransmitters. Indeed, numerous extracellular messengers act to modulate cellular functions by altering the intracellular level of cAMP through increasing the rate of cAMP synthesis by adenylyl cyclases (ACs) or the rate of cAMP hydrolysis by cyclic nucleotide phosphodiesterases (PDEs). While early models proposed that cAMP was uniformly distributed throughout the cell, recent evidence is consistent with the idea that anchoring PDEs to selective subcellular locals may allow control of individual isolated subcellular pools of cAMP. In these studies, we demonstrate that human PDE3B can be targeted to distinct subcellular structures involved in regulating cAMP effects in hematopoietic cell lines, and that this signaling complex regulates the activity of a cAMP‐activated phospholipase C, PLC‐epsilon. In addition, this work is consistent with the novel idea that the regulation of PLC‐epsilon by PDE3B is mediated through effects on the activity of the exchange proteins activated by cAMP (EPACs), and not the more prototyipcal cAMP effector Protein Kinse A (PKA). Our data are presented in the context of PDE3B expression within a multi‐protein cellular complex and indicates PDE‐inhibitor effects in these cells. Funded by HSFO & CIHR