| Autor: |
Laliberté, France, Liu, Susana, Gorseth, Elise, Bobechko, Brian, Bartlett, Adrienne, Lario, Paula, Gresser, Michael J., Huang, Zheng |
| Předmět: |
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| Zdroj: |
FEBS Letters; Feb2002, Vol. 512 Issue 1-3, p205, 4p |
| Abstrakt: |
The PDE4 catalytic machinery comprises, in part, two divalent cations in a binuclear motif. Here we report that PDE4A4 expressed in Sf9 cells exhibits a biphasic Mg2+ dose–response (EC50 of ∼0.15 and >10 mM) in catalyzing cAMP hydrolysis. In vitro phosphorylation of PDE4A4 by the PKA-catalytic subunit increases the enzyme’s sensitivity to Mg2+, leading to 4-fold increased cAMP hydrolysis without affecting its Km. The phosphorylation also increases the potencies of (R)- and (S)-rolipram without affecting CDP-840 and SB-207499. The results support that modulating the cofactor binding affinity of PDE4 represents a mechanism for regulating its activity. [Copyright &y& Elsevier] |
| Databáze: |
Complementary Index |
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