HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 290/1/C123    most recent 00142.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (25) Citing Articles via Google Scholar Google Scholar Articles by Heo, J. S. Articles by Han, H. J. Search for Related Content PubMed PubMed Citation Articles by Heo, J. S. Articles by Han, H. J.

GROWTH, DIFFERENTIATION, AND APOPTOSIS

EGF stimulates proliferation of mouse embryonic stem cells: involvement of Ca²⁺ influx and p44/42 MAPKs

Department of Veterinary Physiology, College of Veterinary Medicine, Chonnam National University, Gwangju, Korea

Submitted 25 March 2005 ; accepted in final form 15 August 2005

We examined the effect of EGF on the proliferation of mouse embryonic stem (ES) cells and their related signal pathways. EGF increased [³H]thymidine and 5-bromo-2'-deoxyuridine incorporation in a time- and dose-dependent manner. EGF stimulated the phosphorylation of EGF receptor (EGFR). Inhibition of EGFR tyrosine kinase with AG-1478 or herbimycin A, inhibition of PLC with neomycin or U-73122, inhibition of PKC with bisindolylmaleimide I or staurosporine, and inhibition of L-type Ca²⁺ channels with nifedipine or methoxyverapamil prevented EGF-induced [³H]thymidine incorporation. PKC-, -_I, -, -, and - were translocated to the membrane and intracellular Ca²⁺ concentration ([Ca²⁺]_i) was increased in response to EGF. Moreover, inhibition of EGFR tyrosine kinase, PLC, and PKC completely prevented EGF-induced increases in [Ca²⁺]_i. EGF also increased inositol phosphate levels, which were blocked by EGFR tyrosine kinase inhibitors. Furthermore, EGF rapidly increased formation of H₂O₂, and pretreatment with antioxidant (N-acetyl-L-cysteine) inhibited EGF-induced increase of [Ca²⁺]_i. In addition, we observed that p44/42 MAPK phosphorylation by EGF and inhibition of EGFR tyrosine kinase, PLC, PKC, or Ca²⁺ channels blocked EGF-induced phosphorylation of p44/42 MAPKs. Inhibition of p44/42 MAPKs with PD-98059 (MEK inhibitor) attenuated EGF-induced increase of [³H]thymidine incorporation. Finally, inhibition of EGFR tyrosine kinase, PKC, Ca²⁺ channels, or p44/42 MAPKs attenuated EGF-stimulated cyclin D1, cyclin E, cyclin-dependent kinase (CDK)2, and CDK4, respectively. In conclusion, EGF partially stimulates proliferation of mouse ES cells via PLC/PKC, Ca²⁺ influx, and p44/42 MAPK signal pathways through EGFR tyrosine kinase phosphorylation.

calcium; epidermal growth factor; mitogen-activated protein kinases; protein kinase C

This article has been cited by other articles:

				J. H. Park and H. J. Han Caveolin-1 plays important role in EGF-induced migration and proliferation of mouse embryonic stem cells: involvement of PI3K/Akt and ERK Am J Physiol Cell Physiol, October 1, 2009; 297(4): C935 - C944. [Abstract] [Full Text] [PDF]

				S. Below, A. Konkel, C. Zeeck, C. Muller, C. Kohler, S. Engelmann, and J.-P. Hildebrandt Virulence factors of Staphylococcus aureus induce Erk-MAP kinase activation and c-Fos expression in S9 and 16HBE14o- human airway epithelial cells Am J Physiol Lung Cell Mol Physiol, March 1, 2009; 296(3): L470 - L479. [Abstract] [Full Text] [PDF]

				S. P. Yun, M. Y. Lee, J. M. Ryu, C. H. Song, and H. J. Han Role of HIF-1{alpha} and VEGF in human mesenchymal stem cell proliferation by 17{beta}-estradiol: involvement of PKC, PI3K/Akt, and MAPKs Am J Physiol Cell Physiol, February 1, 2009; 296(2): C317 - C326. [Abstract] [Full Text] [PDF]

				V. Aires, A. Hichami, R. Filomenko, A. Ple, C. Rebe, A. Bettaieb, and N. A. Khan Docosahexaenoic Acid Induces Increases in [Ca2+]i via Inositol 1,4,5-Triphosphate Production and Activates Protein Kinase C{gamma} and -{delta} via Phosphatidylserine Binding Site: Implication in Apoptosis in U937 Cells Mol. Pharmacol., December 1, 2007; 72(6): 1545 - 1556. [Abstract] [Full Text] [PDF]

				N. Kapur, G. A. Mignery, and K. Banach Cell cycle-dependent calcium oscillations in mouse embryonic stem cells Am J Physiol Cell Physiol, April 1, 2007; 292(4): C1510 - C1518. [Abstract] [Full Text] [PDF]