In vitro PKA phosphorylation-mediated human PDE4A4 activation

被引：17

作者：

Laliberté, F ^{[1
]}

Liu, S ^{[1
]}

Gorseth, E ^{[1
]}

Bobechko, B ^{[1
]}

Bartlett, A ^{[1
]}

Lario, P ^{[1
]}

Gresser, MJ ^{[1
]}

Huang, Z ^{[1
]}

机构：

[1] Merck Frosst Ctr Therapeut Res, Dept Biochem & Mol Biol, Pointe Claire, PQ H9R 4P8, Canada

来源：

FEBS LETTERS | 2002年 / 512卷 / 1-3期

关键词：

PDE4; PKA; phosphorylation; Mg2+; rolipram;

D O I：

10.1016/S0014-5793(02)02259-7

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 similar to 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 K-m. 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. (C) 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.

引用

页码：205 / 208

页数：4

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