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Selective modulation of MAP kinase in embryonic palate cells
M B Potchinsky1, M R Lloyd, W M Weston
1Department of Pathology, Anatomy & Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Journal of Cellular Physiology
|July 2, 1998
Summary
Epidermal growth factor (EGF) stimulates mitogen-activated protein kinase (MAPK) in embryonic palate cells, but other factors inhibiting growth do not solely rely on this pathway. This suggests a dissociation between proliferation and MAPK activation in palatal development.
Area of Science:
- Cellular and Molecular Biology
- Developmental Biology
- Signal Transduction
Background:
- Murine embryonic palate mesenchyme (MEPM) cells respond to various local embryonic factors.
- Cyclic AMP (cAMP) and transforming growth factor beta (TGFbeta) pathways modulate MEPM cell proliferation in response to epidermal growth factor (EGF).
- The mitogen-activated protein kinase (MAPK) cascade is a key pathway mediating cellular responses to EGF.
Purpose of the Study:
- To investigate whether signaling pathways that inhibit EGF-stimulated proliferation do so via the p42/p44 MAPK pathway.
- To elucidate the role of MAPK cascade in mediating growth inhibitory signals in MEPM cells.
- To understand the interplay between different signaling pathways and MAPK activation in palatal cell proliferation.
Main Methods:
- Stimulation of MEPM cells with EGF, TGFbeta, cholera toxin, calcium ionophore A23187, and phorbol ester.
- Assay of MAPK phosphorylation and activity.
- Inhibition studies using MEK inhibitor PD098059 and depletion of protein kinase C (PKC) isozymes.
Main Results:
- EGF rapidly stimulated MAPK phosphorylation and activity in MEPM cells.
- TGFbeta and cholera toxin did not affect EGF-induced MAPK phosphorylation or activity.
- Calcium mobilization reduced EGF-induced proliferation but increased MAPK phosphorylation without a corresponding increase in activity; phorbol ester increased MAPK phosphorylation and activity but inhibited growth.
- MEK and PKC inhibition partially abrogated EGF-induced MAPK phosphorylation, while combined inhibition markedly decreased MAPK activity, indicating EGF utilizes multiple pathways to activate MAPK.
- The MAPK cascade did not mediate signal transduction for several growth-inhibitory agents, showing a dissociation between proliferation and MAPK activation.
Conclusions:
- The MAPK cascade is not the sole mediator for all EGF-induced proliferative or inhibitory signals in MEPM cells.
- There is a dissociation between the proliferative response and MAPK activation for certain signaling pathways.
- Other signaling pathways crucial for palatal tissue differentiation converge with the MAPK cascade, potentially regulating alternative cellular processes.