The cyclic nucleotide phosphodiesterases are crucial components in the regulation of the signal transduction cascades mediated by cAMP and cGMP. The size of this family of enzymes and the complexity of their regulation may not be adequately appreciated. The importance of studying them stems from their intrinsic biochemical and biological interest and from the fact that they are the targets of anti-asthmatic, anti-thrombolytic, cardiotonic, and anti-depressant drugs. Although they have been studied at the biochemical level for many years, the cDNAs and genes of some isoforms have been difficult to clone and this has now become a necessity. We have developed a genetic selection procedure that allows recovery of cDNAs coding for these enzymes. Conditions have been created in which lambda lysogens of E. coli that are capable of expressing a functional cyclic nucleotide or cGMP phosphodiesterase can grow. This method has been used to recover cDNAs that may code for a cGMP stimulated cGMP specific phosphodiesterase from Dictyostelium discoideum. The cGMP mediated signal transduction cascade and this phosphodiesterase regulate the motility of this organism and will be used to ask questions about how cGMP mediated signal transduction controls mobilization of the cytoskeleton and other developmentally important events. The same selection procedure will be improved and extended to recover selected mammalian phosphodiesterase cDNAs and to study their molecular, biochemical, and pharmacological properties.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM046999-03
Application #
2184470
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1992-02-01
Project End
1996-01-31
Budget Start
1994-02-01
Budget End
1995-01-31
Support Year
3
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027