In vitro PKA phosphorylation-mediated human PDE4A4 activation.

Abstract:

: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 Mg(2+) dose-response (EC(50) 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 Mg(2+), 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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Laliberté F,Liu S,Gorseth E,Bobechko B,Bartlett A,Lario P,Gresser MJ,Huang Z

doi

10.1016/s0014-5793(02)02259-7

keywords:

subject

Has Abstract

pub_date

2002-02-13 00:00:00

pages

205-8

issue

1-3

eissn

0014-5793

issn

1873-3468

pii

S0014579302022597

journal_volume

512

pub_type

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