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

 Previous Article  |  Next Article 

Mol Cell Biol. 1991 October; 11(10): 5364-5371

The tumor promoter 12-O-tetradecanoylphorbol-13-acetate and the ras oncogene modulate expression and phosphorylation of gap junction proteins.

Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510.

ABSTRACT

Gap junctional intercellular communication is inhibited in response to tumor promoters and oncogene transformation, suggesting that loss of this function is an important step in tumor formation. To elucidate the molecular mechanisms responsible for this inhibition, we examined the expression of gap junction proteins and mRNA in mouse primary keratinocytes after treatment with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and/or ras transformation. During normal cell growth, keratinocytes expression the alpha 1 (connexin 43) and beta 2 (connexin 26) proteins. Within 5 min of TPA treatment, the alpha 1 protein became rapidly phosphorylated on serine residues and its expression was dramatically reduced by 24 h. The beta 2 protein, after an initial increase in expression, was also significantly reduced 24 h after treatment with TPA. ras transformation caused changes similar to those induced by TPA. The alpha 1 protein underwent an increase in serine phosphorylation, although its expression declined only slightly, while beta 2 expression was greatly reduced. The effects of TPA and ras on alpha 1 expression were additive; treatment of ras-transformed cells with TPA resulted in increased alpha 1 phosphorylation, with greatly decreased protein levels, much lower than those generated by either agent alone. These data provide a likely explanation for the similar and synergistic inhibition of gap junctional intercellular communication by phorbol esters and ras.

This article has been cited by other articles:

• Tanmahasamut, P., Sidell, N. (2005). Up-Regulation of Gap Junctional Intercellular Communication and Connexin43 Expression by Retinoic Acid in Human Endometrial Stromal Cells. J. Clin. Endocrinol. Metab. 90: 4151-4156 [Abstract] [Full Text]  
• Aravindakshan, J., Cyr, D. G. (2005). Nonylphenol Alters Connexin 43 Levels and Connexin 43 Phosphorylation Via an Inhibition of the p38-Mitogen-Activated Protein Kinase Pathway. Biol. Reprod. 72: 1232-1240 [Abstract] [Full Text]  
• Leithe, E., Rivedal, E. (2004). Ubiquitination and Down-regulation of Gap Junction Protein Connexin-43 in Response to 12-O-Tetradecanoylphorbol 13-Acetate Treatment. J. Biol. Chem. 279: 50089-50096 [Abstract] [Full Text]  
• Richards, T. S., Dunn, C. A., Carter, W. G., Usui, M. L., Olerud, J. E., Lampe, P. D. (2004). Protein kinase C spatially and temporally regulates gap junctional communication during human wound repair via phosphorylation of connexin43 on serine368. J. Cell Biol. 167: 555-562 [Abstract] [Full Text]  
• Kretz, M., Euwens, C., Hombach, S., Eckardt, D., Teubner, B., Traub, O., Willecke, K., Ott, T. (2003). Altered connexin expression and wound healing in the epidermis of connexin-deficient mice. J. Cell Sci. 116: 3443-3452 [Abstract] [Full Text]  
• Leithe, E., Cruciani, V., Sanner, T., Mikalsen, S.-O., Rivedal, E. (2003). Recovery of gap junctional intercellular communication after phorbol ester treatment requires proteasomal degradation of protein kinase C. Carcinogenesis 24: 1239-1245 [Abstract] [Full Text]  
• Solan, J. L., Fry, M. D., TenBroek, E. M., Lampe, P. D. (2003). Connexin43 phosphorylation at S368 is acute during S and G2/M and in response to protein kinase C activation. J. Cell Sci. 116: 2203-2211 [Abstract] [Full Text]  
• Carystinos, G. D., Kandouz, M., Alaoui-Jamali, M. A., Batist, G. (2003). Unexpected Induction of the Human Connexin 43 Promoter by the Ras Signaling Pathway Is Mediated by a Novel Putative Promoter Sequence. Mol. Pharmacol. 63: 821-831 [Abstract] [Full Text]  
• Jahromi, S. S., Wentlandt, K., Piran, S., Carlen, P. L. (2002). Anticonvulsant Actions of Gap Junctional Blockers in an In Vitro Seizure Model. J. Neurophysiol. 88: 1893-1902 [Abstract] [Full Text]  
• Martinez, A. D., Hayrapetyan, V., Moreno, A. P., Beyer, E. C. (2002). Connexin43 and Connexin45 Form Heteromeric Gap Junction Channels in Which Individual Components Determine Permeability and Regulation. Circ. Res. 90: 1100-1107 [Abstract] [Full Text]  
• Bruzzone, S., Franco, L., Guida, L., Zocchi, E., Contini, P., Bisso, A., Usai, C., De Flora, A. (2001). A Self-restricted CD38-connexin 43 Cross-talk Affects NAD+ and Cyclic ADP-ribose Metabolism and Regulates Intracellular Calcium in 3T3 Fibroblasts. J. Biol. Chem. 276: 48300-48308 [Abstract] [Full Text]  
• Lampe, P. D., Qiu, Q., Meyer, R. A., TenBroek, E. M., Walseth, T. F., Starich, T. A., Grunenwald, H. L., Johnson, R. G. (2001). Gap junction assembly: PTX-sensitive G proteins regulate the distribution of connexin43 within cells. Am. J. Physiol. Cell Physiol. 281: C1211-C1222 [Abstract] [Full Text]  
• Lampe, P. D., TenBroek, E. M., Burt, J. M., Kurata, W. E., Johnson, R. G., Lau, A. F. (2000). Phosphorylation of Connexin43 on Serine368 by Protein Kinase C Regulates Gap Junctional Communication. J. Cell Biol. 149: 1503-1512 [Abstract] [Full Text]  
• Laird, D. W., Fistouris, P., Batist, G., Alpert, L., Huynh, H. T., Carystinos, G. D., Alaoui-Jamali, M. A. (1999). Deficiency of Connexin43 Gap Junctions Is an Independent Marker for Breast Tumors. Cancer Res. 59: 4104-4110 [Abstract] [Full Text]  
• Woodruff, M. L., Chaban, V. V., Worley, C. M., Dirksen, E. R. (1999). PKC role in mechanically induced Ca2+ waves and ATP-induced Ca2+ oscillations in airway epithelial cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 276: L669-L678 [Abstract] [Full Text]  
• Risek, B, Pozzi, A, Gilula, N. (1998). Modulation of gap junction expression during transient hyperplasia of rat epidermis. J. Cell Sci. 111: 1395-1404 [Abstract]  
• Lampe, P., Kurata, W., Warn-Cramer, B., Lau, A. (1998). Formation of a distinct connexin43 phosphoisoform in mitotic cells is dependent upon p34cdc2 kinase. J. Cell Sci. 111: 833-841 [Abstract]  
• Xie, H.-q., Laird, D. W., Chang, T.-H., Hu, V. W. (1997). A Mitosis-specific Phosphorylation of the Gap Junction Protein Connexin43 in Human Vascular Cells: Biochemical Characterization and Localization. J. Cell Biol. 137: 203-210 [Abstract] [Full Text]  
• Wang, Y, Rose, B (1997). An inhibition of gap-junctional communication by cadherins. J. Cell Sci. 110: 301-309 [Abstract]  
• Warn-Cramer, B. J., Lampe, P. D., Kurata, W. E., Kanemitsu, M. Y., Loo, L. W. M., Eckhart, W., Lau, A. F. (1996). Characterization of the Mitogen-activated Protein Kinase Phosphorylation Sites on the Connexin-43 Gap Junction Protein. J. Biol. Chem. 271: 3779-3786 [Abstract] [Full Text]  
• Wang, Y., Mehta, P. P., Rose, , B. (1995). Inhibition of Glycosylation Induces Formation of Open Connexin-43 Cell-to-Cell Channels and Phosphorylation and Triton X-100 Insolubility of Connexin-43. J. Biol. Chem. 270: 26581-26585 [Abstract] [Full Text]  
• Andersen, J., Barbieri, R. L. (1995). Abnormal Gene Expression in Uterine Leiomyomas. Reproductive Sciences 2: 663-672 [Abstract]  
• Loo, L. W. M., Berestecky, J. M., Kanemitsu, M. Y., Lau, A. F. (1995). pp60[IMAGE] -mediated Phosphorylation of Connexin 43, a Gap Junction Protein. J. Biol. Chem. 270: 12751-12761 [Abstract] [Full Text]  
• Kumar, N., Friend, D., Gilula, N. (1995). Synthesis and assembly of human beta 1 gap junctions in BHK cells by DNA transfection with the human beta 1 cDNA. J. Cell Sci. 108: 3725-3734 [Abstract]  
• Wang, Y, Rose, B (1995). Clustering of Cx43 cell-to-cell channels into gap junction plaques: regulation by cAMP and microfilaments. J. Cell Sci. 108: 3501-3508 [Abstract]  
• Atkinson, M., Lampe, P., Lin, H., Kollander, R, Li, X., Kiang, D. (1995). Cyclic AMP modifies the cellular distribution of connexin43 and induces a persistent increase in the junctional permeability of mouse mammary tumor cells. J. Cell Sci. 108: 3079-3090 [Abstract]