The unique N-terminal domain of the cAMP phosphodiesterase PDE4D4 allows for interaction with specific SH3 domains

• Published in: FEBS letters 1999-10, Vol.460 (1), p.173-177
• Main Authors: Beard, Matthew B., O’Connell, Jonathan C., Bolger, Graeme B., Houslay, Miles D.
• Format: Article
• Language: English
• Subjects: 3',5'-Cyclic-AMP Phosphodiesterases - chemistry; Amino Acid Sequence; Animals; Brain - enzymology; cAMP phosphodiesterase; Carrier Proteins - genetics; Compartmentalisation; Cyclic AMP - pharmacology; Cyclic Nucleotide Phosphodiesterases, Type 3; Cyclic Nucleotide Phosphodiesterases, Type 4; Humans; Isoenzymes - metabolism; Lyn; Maltose-Binding Proteins; Molecular Sequence Data; PDE, cyclic nucleotide phosphodiesterase; Protein Binding; Protein-protein interaction; Rats; Recombinant Fusion Proteins - metabolism; SH3, src homology 3 domain; Src family tyrosyl kinase; Src homology 3 domain; src Homology Domains - genetics; src-Family Kinases - metabolism; UCR, upstream conserved region
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(99)01335-6

Of the five PDE4D isoenzymes, only the PDE4D4 cAMP specific phosphodiesterase was able to bind to SH3 domains. Only PDE4D4 and PDE4A5, but not any other PDE4A, B, C and D isoforms expressed in rat brain, bound to src, lyn and fyn kinase SH3 domains. Purified PDE4D4 could bind to purified lyn SH3. PDE4D4 and PDE4A5 both exhibited selectivity for binding the SH3 domains of certain proteins. PDE4D4 did not bind to WW domains. We suggest that an important function of the unique N-terminal region of PDE4D4 may be to allow for association with certain SH3 domain-containing proteins.