1. Stimulation of p70S6 kinase via a growth hormone-controlled phosphatidylinositol 3-kinase pathway leads to the activation of a PDE4A cyclic AMP-specific phosphodiesterase in 3T3-F442A preadipocytes
- Author
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Graeme B. Bolger, Richard G. Vernon, Simon J. MacKenzie, Miles D. Houslay, Alexander H. Peden, and Stephen J. Yarwood
- Subjects
Cellular differentiation ,Molecular Sequence Data ,Phosphatidylinositol 3-Kinases ,Biology ,Cell Line ,chemistry.chemical_compound ,Mice ,medicine ,Adipocytes ,Animals ,Phosphatidylinositol ,Protein kinase C ,Rolipram ,Multidisciplinary ,Kinase ,Ribosomal Protein S6 Kinases ,Phosphodiesterase ,Cell Differentiation ,Biological Sciences ,Fibroblasts ,Molecular biology ,Cyclic Nucleotide Phosphodiesterases, Type 4 ,Enzyme Activation ,chemistry ,3',5'-Cyclic-AMP Phosphodiesterases ,Growth Hormone ,Signal transduction ,medicine.drug ,Signal Transduction - Abstract
The challenge of 3T3-F442A fibroblasts with growth hormone led to both a decrease in the mobility on SDS/PAGE and activation of the PDE4A cyclic AMP-specific phosphodiesterase isoform PDE4A5. Activation was mediated by a JAK-2-dependent pathway coupled to the activation of phosphatidylinositol 3-kinase and p70S6 kinase. Activation was not dependent on the ability of growth hormone to stimulate ERK2 or protein kinase C or any effect on transcription. Blockade of activation of murine PDE4A5 ablated the ability of growth hormone to decrease intracellular cAMP levels. Antisense depletion of murine PDE4A5 mimicked the ability of rolipram to enhance the growth hormone-stimulated differentiation of 3T3-F442A cells to adipocytes. It is suggested that activation of PDE4A5 by growth hormone serves as a brake on the differentiation processes.
- Published
- 1998