Investigation of extracellular signal-regulated kinase 2 mitogen-activated protein kinase phosphorylation and regulation of activity of PDE4 cyclic adenosine monophosphate-specific phosphodiesterases.
Recently, it has been shown that enzymes of the cyclic adenosine monophosphate (cAMP)-specific phosphodiesterase (PDE) family 4 can be directly phosphorylated by extracellular signal-regulated kinase 2 (ERK2). Phosphorylation of PDE4s by ERK2 is dependent on two docking domains on either side of the target serine that allow specificity and high-fidelity binding of the kinase. The functional consequence of PDE4 phosphorylation by ERK is either an increase or a decrease in PDE activity, depending on whether the PDE4 contains only one of the upstream conserved regions (UCR1) that are typical of PDE4s or both (UCR1 and UCR2). We detail some of the methods that have been crucial in elucidating these important discoveries that represent a novel point of cross talk between the cAMP signaling system and the ERK mitogen-activated protein kinase cascade.
Molecular Pharmacology Group, Division of Biochemistry and Molecular Biology, Lund University, Biomedical Center, Sweden.
Elaine V
EV
Hill
Miles D
MD
Houslay
George S
GS
Baillie
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D020134:Catalytic Domain / Q000235:genetics / Q000502:physiology; D002522:Chlorocebus aethiops; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D010766:Phosphorylation; D015290:Second Messenger Systems / Q000235:genetics / Q000502:physiology*
D019950:Mitogen-Activated Protein Kinase 1; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4