This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Viñals, F.
Right arrow Articles by Pouysségur, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Viñals, F.
Right arrow Articles by Pouysségur, J.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, April 1999, p. 2763-2772, Vol. 19, No. 4
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Confluence of Vascular Endothelial Cells Induces Cell Cycle Exit by Inhibiting p42/p44 Mitogen-Activated Protein Kinase Activity

Francesc Viñals* and Jacques Pouysségur

Centre de Biochimie-CNRS UMR 6543, Université de Nice, 06108 Nice, France

Received 10 September 1998/Returned for modification 9 November 1998/Accepted 6 January 1999

Like other cellular models, endothelial cells in cultures stop growing when they reach confluence, even in the presence of growth factors. In this work, we have studied the effect of cellular contact on the activation of p42/p44 mitogen-activated protein kinase (MAPK) by growth factors in mouse vascular endothelial cells. p42/p44 MAPK activation by fetal calf serum or fibroblast growth factor was restrained in confluent cells in comparison with the activity found in sparse cells. Consequently, the induction of c-fos, MAPK phosphatases 1 and 2 (MKP1/2), and cyclin D1 was also restrained in confluent cells. In contrast, the activation of Ras and MEK-1, two upstream activators of the p42/p44 MAPK cascade, was not impaired when cells attained confluence. Sodium orthovanadate, but not okadaic acid, restored p42/p44 MAPK activity in confluent cells. Moreover, lysates from confluent 1G11 cells more effectively inactivated a dually phosphorylated active p42 MAPK than lysates from sparse cells. These results, together with the fact that vanadate-sensitive phosphatase activity was higher in confluent cells, suggest that phosphatases play a role in the down-regulation of p42/p44 MAPK activity. Enforced long-term activation of p42/p44 MAPK by expression of the chimera Delta Raf-1:ER, which activates the p42/p44 MAPK cascade at the level of Raf, enhanced the expression of MKP1/2 and cyclin D1 and, more importantly, restored the reentry of confluent cells into the cell cycle. Therefore, inhibition of p42/p44 MAPK activation by cell-cell contact is a critical step initiating cell cycle exit in vascular endothelial cells.

* Corresponding author. Mailing address: Centre de Biochimie-CNRS UMR 6543, Université de Nice, Parc Valrose, 06108 Nice, France. Phone: 33-4-92 07 64 27. Fax: 33-4-92 07 64 32. E-mail: vinals{at}unice.fr.

Molecular and Cellular Biology, April 1999, p. 2763-2772, Vol. 19, No. 4
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Chaturvedi, P., Singh, A. P., Batra, S. K. (2008). Structure, evolution, and biology of the MUC4 mucin. FASEB J. 22: 966-981 [Abstract] [Full Text]  
  • Risinger, G. M. Jr., Hunt, T. S., Updike, D. L., Bullen, E. C., Howard, E. W. (2006). Matrix Metalloproteinase-2 Expression by Vascular Smooth Muscle Cells Is Mediated by Both Stimulatory and Inhibitory Signals in Response to Growth Factors. J. Biol. Chem. 281: 25915-25925 [Abstract] [Full Text]  
  • Davis, G. E., Senger, D. R. (2005). Endothelial Extracellular Matrix: Biosynthesis, Remodeling, and Functions During Vascular Morphogenesis and Neovessel Stabilization. Circ. Res. 97: 1093-1107 [Abstract] [Full Text]  
  • Tiffin, N., Adi, S., Stokoe, D., Wu, N.-Y., Rosenthal, S. M. (2004). Akt Phosphorylation Is Not Sufficient for Insulin-Like Growth Factor-Stimulated Myogenin Expression but Must Be Accompanied by Down-Regulation of Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Phosphorylation. Endocrinology 145: 4991-4996 [Abstract] [Full Text]  
  • Wadgaonkar, R., Pierce, J. W., Somnay, K., Damico, R. L., Crow, M. T., Collins, T., Garcia, J. G. N. (2004). Regulation of c-Jun N-terminal Kinase and p38 Kinase Pathways in Endothelial Cells. Am. J. Respir. Cell Mol. Bio. 31: 423-431 [Abstract] [Full Text]  
  • Li, S., Gerrard, E. R. Jr., Balkovetz, D. F. (2004). Evidence for ERK1/2 phosphorylation controlling contact inhibition of proliferation in Madin-Darby canine kidney epithelial cells. Am. J. Physiol. Cell Physiol. 287: C432-C439 [Abstract] [Full Text]  
  • Ning, W., Chu, T. J., Li, C. J., Choi, A. M. K., Peters, D. G. (2004). Genome-wide analysis of the endothelial transcriptome under short-term chronic hypoxia. Physiol. Genomics 18: 70-78 [Abstract] [Full Text]  
  • McMorran, B., Town, L., Costelloe, E., Palmer, J., Engel, J., Hume, D., Wainwright, B. (2003). Effector ExoU from the Type III Secretion System Is an Important Modulator of Gene Expression in Lung Epithelial Cells in Response to Pseudomonas aeruginosa Infection. Infect. Immun. 71: 6035-6044 [Abstract] [Full Text]  
  • Lampugnani, M. G., Zanetti, A., Corada, M., Takahashi, T., Balconi, G., Breviario, F., Orsenigo, F., Cattelino, A., Kemler, R., Daniel, T. O., Dejana, E. (2003). Contact inhibition of VEGF-induced proliferation requires vascular endothelial cadherin, {beta}-catenin, and the phosphatase DEP-1/CD148. JCB 161: 793-804 [Abstract] [Full Text]  
  • Deroanne, C., Vouret-Craviari, V., Wang, B., Pouyssegur, J. (2003). EphrinA1 inactivates integrin-mediated vascular smooth muscle cell spreading via the Rac/PAK pathway. J. Cell Sci. 116: 1367-1376 [Abstract] [Full Text]  
  • Zanetti, A., Lampugnani, M. G., Balconi, G., Breviario, F., Corada, M., Lanfrancone, L., Dejana, E. (2002). Vascular Endothelial Growth Factor Induces Shc Association With Vascular Endothelial Cadherin: A Potential Feedback Mechanism to Control Vascular Endothelial Growth Factor Receptor-2 Signaling. Arterioscler. Thromb. Vasc. Bio. 22: 617-622 [Abstract] [Full Text]  
  • Kanthou, C., Tozer, G. M. (2002). The tumor vascular targeting agent combretastatin A-4-phosphate induces reorganization of the actin cytoskeleton and early membrane blebbing in human endothelial cells. Blood 99: 2060-2069 [Abstract] [Full Text]  
  • Adi, S., Bin-Abbas, B., Wu, N.-Y., Rosenthal, S. M. (2002). Early Stimulation and Late Inhibition of Extracellular Signal-Regulated Kinase 1/2 Phosphorylation by IGF-I: A Potential Mechanism Mediating the Switch in IGF-I Action on Skeletal Muscle Cell Differentiation. Endocrinology 143: 511-516 [Abstract] [Full Text]  
  • Senger, D. R., Perruzzi, C. A., Streit, M., Koteliansky, V. E., de Fougerolles, A. R., Detmar, M. (2002). The {alpha}1{beta}1 and {alpha}2{beta}1 Integrins Provide Critical Support for Vascular Endothelial Growth Factor Signaling, Endothelial Cell Migration, and Tumor Angiogenesis. Am. J. Pathol. 160: 195-204 [Abstract] [Full Text]  
  • Yano, H., Uchida, H., Iwasaki, T., Mukai, M., Akedo, H., Nakamura, K., Hashimoto, S., Sabe, H. (2000). Paxillin alpha and Crk-associated substrate exert opposing effects on cell migration and contact inhibition of growth through tyrosine phosphorylation. Proc. Natl. Acad. Sci. USA 97: 9076-9081 [Abstract] [Full Text]  
  • Suzuki, E., Nagata, D., Yoshizumi, M., Kakoki, M., Goto, A., Omata, M., Hirata, Y. (2000). Reentry into the Cell Cycle of Contact-inhibited Vascular Endothelial Cells by a Phosphatase Inhibitor. POSSIBLE INVOLVEMENT OF EXTRACELLULAR SIGNAL-REGULATED KINASE AND PHOSPHATIDYLINOSITOL 3-KINASE. J. Biol. Chem. 275: 3637-3644 [Abstract] [Full Text]  
  • Vinals, F., Chambard, J. C., Pouyssegur, J. (1999). p70 S6 Kinase-mediated Protein Synthesis Is a Critical Step for Vascular Endothelial Cell Proliferation. J. Biol. Chem. 274: 26776-26782 [Abstract] [Full Text]  
  • Surapisitchat, J., Hoefen, R. J., Pi, X., Yoshizumi, M., Yan, C., Berk, B. C. (2001). Fluid shear stress inhibits TNF-alpha activation of JNK but not ERK1/2 or p38 in human umbilical vein endothelial cells: Inhibitory crosstalk among MAPK family members. Proc. Natl. Acad. Sci. USA 98: 6476-6481 [Abstract] [Full Text]  
  • Zanetti, A., Lampugnani, M. G., Balconi, G., Breviario, F., Corada, M., Lanfrancone, L., Dejana, E. (2002). Vascular Endothelial Growth Factor Induces Shc Association With Vascular Endothelial Cadherin: A Potential Feedback Mechanism to Control Vascular Endothelial Growth Factor Receptor-2 Signaling. Arterioscler. Thromb. Vasc. Bio. 22: 617-622 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»