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
- 31 March 1998
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 95 (7) , 3549-3554
- https://doi.org/10.1073/pnas.95.7.3549
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.Keywords
This publication has 61 references indexed in Scilit:
- Altered Expression of PDE1 and PDE4 Cyclic Nucleotide Phosphodiesterase Isoforms in 7-oxo-prostacyclin-preconditioned Rat HeartJournal of Molecular and Cellular Cardiology, 1997
- The Human Cyclic AMP-specific Phosphodiesterase PDE-46 (HSPDE4A4B) Expressed in Transfected COS7 Cells Occurs as Both Particulate and Cytosolic Species That Exhibit Distinct Kinetics of Inhibition by the Antidepressant RolipramPublished by Elsevier ,1996
- Participation of JAK and STAT Proteins in Growth Hormone-induced SignalingJournal of Biological Chemistry, 1996
- Mitogenic Response to TGF-β in 3T3-F442A CellsBiochemical and Biophysical Research Communications, 1995
- PD 098059 Is a Specific Inhibitor of the Activation of Mitogen-activated Protein Kinase Kinase in Vitro and in VivoJournal of Biological Chemistry, 1995
- Novel functions of phosphatidylinositol 3-kinase in terminally differentiated cellsCellular Signalling, 1995
- Growth Hormone Stimulates the Tyrosine Phosphorylation of the Insulin Receptor Substrate-1 and Its Association with Phosphatidylinositol 3-Kinase in Primary AdipocytesJournal of Biological Chemistry, 1995
- Molecular biology of the cyclic AMP-specific cyclic nucleotide phosphodiesterases: A diverse family of regulatory enzymesCellular Signalling, 1994
- The Generation of Insulin-Like Growth Factor-1—Sensitive Cells by Growth Hormone ActionScience, 1986
- A role for soluble cAMP phosphodiesterases in differentiation of 3T3‐L1 adipocytesJournal of Cellular Physiology, 1985