Heparin Binding Epidermal Growth Factor-Like Growth Factor and PD169316 Prevent Apoptosis in Mouse Embryonic Stem Cells

Apoptosis or programmed cell death is an important outcome of cell fate and is influenced by several factors. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a member of the EGF family of growth factors and is synthesized as a membrane-associated precursor molecule (proHB-EGF)...

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Bibliographic Details
Published in:Journal of biochemistry (Tokyo) 2009-02, Vol.145 (2), p.177-184
Main Authors: Krishnamoorthy, Malini, Heimburg-Molinaro, Jamie, Bargo, Ana M, Nash, Rachel J, Nash, Rodney J
Format: Article
Language:English
Subjects:
Animals
Antigens, CD - metabolism
Apoptosis
CD9
EGFR
Embryo, Mammalian - metabolism
Embryonic Stem Cells - drug effects
Embryonic Stem Cells - metabolism
Enzyme Inhibitors - pharmacology
Fluorescent Antibody Technique
HB-EGF
Heparin-binding EGF-like Growth Factor
Imidazoles - pharmacology
Intercellular Signaling Peptides and Proteins - pharmacology
Membrane Glycoproteins - metabolism
Mice
p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors
p38 Mitogen-Activated Protein Kinases - metabolism
PD169316
Phosphorylation
Regular Papers
RNA Interference
Tetraspanin-29
Transfection
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Summary:Apoptosis or programmed cell death is an important outcome of cell fate and is influenced by several factors. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a member of the EGF family of growth factors and is synthesized as a membrane-associated precursor molecule (proHB-EGF). Under stressful conditions proHB-EGF is proteolytically cleaved and released as a soluble ligand (sHB-EGF) that activates the EGF receptor. We show that antibody against CD9, a membrane tetraspanin, induces apoptosis in mouse embryonic stem cells through the activation of specific EGF receptor residues (Y-1148 and Y-1173), caspase-3 and MAPK signalling. HB-EGF and the p38 inhibitor PD169316 act in a pro-survival manner by perturbing phosphorylation of EGFR Y-1173, suggesting its importance in inducing apoptosis. Caspase-3 activation was attenuated in the presence of HB-EGF and PD169316. Furthermore, HB-EGF and PD169316 prevent p38 phosphorylation while promoting the phosphorylation of the pro-survival SAPK/JNK and ERK. These results suggest a role for CD9 as an endogenous suppressor of apoptosis, an effect that is mimicked by HB-EGF and PD169316.
ISSN:0021-924X
1756-2651
DOI:10.1093/jb/mvn153