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 Zundel, W.
Right arrow Articles by Giaccia, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zundel, W.
Right arrow Articles by Giaccia, A.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, March 2000, p. 1507-1514, Vol. 20, No. 5
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Caveolin 1-Mediated Regulation of Receptor Tyrosine Kinase-Associated Phosphatidylinositol 3-Kinase Activity by Ceramide

Wayne Zundel, Lillian M. Swiersz, and Amato Giaccia*

Cancer Biology Program, Mayer Cancer Biology Research Laboratory, Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California 94305-5468

Previous studies have indicated that proapoptotic stresses downregulate the phosphatidylinositol 3-kinase [PI(3)K]/Akt survival pathway via the activation of acid-sphingomyelinase (A-SMase) and ceramide production. Ceramide induces apoptosis and inhibits PI(3)K activity without altering expression, association, or phosphorylation of receptors, adapter proteins, or PI(3)K subunits. PI(3)K inhibition by ceramide is associated with recruitment of caveolin 1 to PI(3)K-associated receptor complexes within lipid raft microdomains. Overexpression of caveolin 1 alone is sufficient to alter PI(3)K activity and sensitizes fibroblasts to ceramide-induced cell death. Most importantly, antisense expression of caveolin 1 dramatically reduces ceramide-induced PI(3)K deregulation and results in a loss-of-function stress response similar to that in A-SMase-deficient cells. Stress-induced recruitment of caveolin 1 to receptor complexes was found to be dependent on A-SMase since cell lines deficient in A-SMase did not exhibit caveolin 1 association with PI(3)K receptor complexes. Thus, a genetic link between A-SMase activation and caveolin 1-induced inhibition of PI(3)K activity exists. These results led us to propose that stress-induced changes in raft microdomains lead to altered receptor tyrosine kinase signal transduction through the modulation of caveolin 1 by ceramide.

* Corresponding author. Mailing address: CBRL, GK101, Stanford University School of Medicine, Stanford, CA 94305-5468. Phone: (650) 723-7366. Fax: (650) 723-7382. E-mail: giaccia{at}leland.stanford.edu.

Molecular and Cellular Biology, March 2000, p. 1507-1514, Vol. 20, No. 5
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Chanvorachote, P., Nimmannit, U., Lu, Y., Talbott, S., Jiang, B.-H., Rojanasakul, Y. (2009). Nitric Oxide Regulates Lung Carcinoma Cell Anoikis through Inhibition of Ubiquitin-Proteasomal Degradation of Caveolin-1. J. Biol. Chem. 284: 28476-28484 [Abstract] [Full Text]  
  • Liao, W.-x., Feng, L., Zhang, H., Zheng, J., Moore, T. R., Chen, D.-b. (2009). Compartmentalizing VEGF-Induced ERK2/1 Signaling in Placental Artery Endothelial Cell Caveolae: A Paradoxical Role of Caveolin-1 in Placental Angiogenesis in Vitro. Mol. Endocrinol. 23: 1428-1444 [Abstract] [Full Text]  
  • Park, S. E., Jeong, S. H., Yee, S.-B., Kim, T. H., Soung, Y. H., Ha, N. C., Kim, N. D., Park, J.-Y., Bae, H. R., Park, B. S., Lee, H. J., Yoo, Y. H. (2008). Interactions of acetylcholinesterase with caveolin-1 and subsequently with cytochrome c are required for apoptosome formation. Carcinogenesis 29: 729-737 [Abstract] [Full Text]  
  • Volonte, D., McTiernan, C. F., Drab, M., Kasper, M., Galbiati, F. (2008). Caveolin-1 and caveolin-3 form heterooligomeric complexes in atrial cardiac myocytes that are required for doxorubicin-induced apoptosis. Am. J. Physiol. Heart Circ. Physiol. 294: H392-H401 [Abstract] [Full Text]  
  • Reichardt, L. F (2006). Neurotrophin-regulated signalling pathways. Phil Trans R Soc B 361: 1545-1564 [Abstract] [Full Text]  
  • Lu, X., Kambe, F., Cao, X., Yoshida, T., Ohmori, S., Murakami, K., Kaji, T., Ishii, T., Zadworny, D., Seo, H. (2006). DHCR24-Knockout Embryonic Fibroblasts Are Susceptible to Serum Withdrawal-Induced Apoptosis Because of Dysfunction of Caveolae and Insulin-Akt-Bad Signaling. Endocrinology 147: 3123-3132 [Abstract] [Full Text]  
  • Torres, V. A., Tapia, J. C., Rodriguez, D. A., Parraga, M., Lisboa, P., Montoya, M., Leyton, L., Quest, A. F. G. (2006). Caveolin-1 controls cell proliferation and cell death by suppressing expression of the inhibitor of apoptosis protein survivin. J. Cell Sci. 119: 1812-1823 [Abstract] [Full Text]  
  • Gulbins, E., Li, P. L. (2006). Physiological and pathophysiological aspects of ceramide. Am. J. Physiol. Regul. Integr. Comp. Physiol. 290: R11-R26 [Abstract] [Full Text]  
  • Sotgia, F., Williams, T. M., Schubert, W., Medina, F., Minetti, C., Pestell, R. G., Lisanti, M. P. (2006). Caveolin-1 Deficiency (-/-) Conveys Premalignant Alterations in Mammary Epithelia, with Abnormal Lumen Formation, Growth Factor Independence, and Cell Invasiveness. Am. J. Pathol. 168: 292-309 [Abstract] [Full Text]  
  • Williams, T. M., Lisanti, M. P. (2005). Caveolin-1 in oncogenic transformation, cancer, and metastasis. Am. J. Physiol. Cell Physiol. 288: C494-C506 [Abstract] [Full Text]  
  • Beardsley, A., Fang, K., Mertz, H., Castranova, V., Friend, S., Liu, J. (2005). Loss of Caveolin-1 Polarity Impedes Endothelial Cell Polarization and Directional Movement. J. Biol. Chem. 280: 3541-3547 [Abstract] [Full Text]  
  • Bauer, P. M., Yu, J., Chen, Y., Hickey, R., Bernatchez, P. N., Looft-Wilson, R., Huang, Y., Giordano, F., Stan, R. V., Sessa, W. C. (2005). Endothelial-specific expression of caveolin-1 impairs microvascular permeability and angiogenesis. Proc. Natl. Acad. Sci. USA 102: 204-209 [Abstract] [Full Text]  
  • Liu, Q., Moller, U., Flugel, D., Kietzmann, T. (2004). Induction of plasminogen activator inhibitor I gene expression by intracellular calcium via hypoxia-inducible factor-1. Blood 104: 3993-4001 [Abstract] [Full Text]  
  • Gonzalez, E., Nagiel, A., Lin, A. J., Golan, D. E., Michel, T. (2004). Small Interfering RNA-mediated Down-regulation of Caveolin-1 Differentially Modulates Signaling Pathways in Endothelial Cells. J. Biol. Chem. 279: 40659-40669 [Abstract] [Full Text]  
  • Ono, K., Iwanaga, Y., Hirayama, M., Kawamura, T., Sowa, N., Hasegawa, K. (2004). Contribution of caveolin-1{alpha} and Akt to TNF-{alpha}-induced cell death. Am. J. Physiol. Lung Cell. Mol. Physiol. 287: L201-L209 [Abstract] [Full Text]  
  • Li, L., Ren, C. H., Tahir, S. A., Ren, C., Thompson, T. C. (2003). Caveolin-1 Maintains Activated Akt in Prostate Cancer Cells through Scaffolding Domain Binding Site Interactions with and Inhibition of Serine/Threonine Protein Phosphatases PP1 and PP2A. Mol. Cell. Biol. 23: 9389-9404 [Abstract] [Full Text]  
  • Igarashi, J., Erwin, P. A., Dantas, A. P. V., Chen, H., Michel, T. (2003). VEGF induces S1P1 receptors in endothelial cells: Implications for cross-talk between sphingolipid and growth factor receptors. Proc. Natl. Acad. Sci. USA 100: 10664-10669 [Abstract] [Full Text]  
  • Li, Y.-Q., Chen, P., Haimovitz-Friedman, A., Reilly, R. M., Wong, C. S. (2003). Endothelial Apoptosis Initiates Acute Blood-Brain Barrier Disruption after Ionizing Radiation. Cancer Res. 63: 5950-5956 [Abstract] [Full Text]  
  • Assa-Kunik, E., Fishman, D., Kellman-Pressman, S., Tsory, S., Elhyany, S., Baharir, O., Segal, S. (2003). Alterations in the Expression of MHC Class I Glycoproteins by B16BL6 Melanoma Cells Modulate Insulin Receptor-Regulated Signal Transduction and Augments Resistance to Apoptosis. J. Immunol. 171: 2945-2952 [Abstract] [Full Text]  
  • Gargalovic, P., Dory, L. (2003). Cellular apoptosis is associated with increased caveolin-1 expression in macrophages. J. Lipid Res. 44: 1622-1632 [Abstract] [Full Text]  
  • Peterson, T. E., Guicciardi, M. E., Gulati, R., Kleppe, L. S., Mueske, C. S., Mookadam, M., Sowa, G., Gores, G. J., Sessa, W. C., Simari, R. D. (2003). Caveolin-1 Can Regulate Vascular Smooth Muscle Cell Fate by Switching Platelet-Derived Growth Factor Signaling From a Proliferative to an Apoptotic Pathway. Arterioscler. Thromb. Vasc. Bio. 23: 1521-1527 [Abstract] [Full Text]  
  • Oshikawa, J., Toya, Y., Fujita, T., Egawa, M., Kawabe, J., Umemura, S., Ishikawa, Y. (2003). Nicotinic acetylcholine receptor {alpha}7 regulates cAMP signal within lipid rafts. Am. J. Physiol. Cell Physiol. 285: C567-C574 [Abstract] [Full Text]  
  • Shack, S., Wang, X.-T., Kokkonen, G. C., Gorospe, M., Longo, D. L., Holbrook, N. J. (2003). Caveolin-Induced Activation of the Phosphatidylinositol 3-Kinase/Akt Pathway Increases Arsenite Cytotoxicity. Mol. Cell. Biol. 23: 2407-2414 [Abstract] [Full Text]  
  • Williams, T. M., Cheung, M. W.-C., Park, D. S., Razani, B., Cohen, A. W., Muller, W. J., Di Vizio, D., Chopra, N. G., Pestell, R. G., Lisanti, M. P. (2003). Loss of Caveolin-1 Gene Expression Accelerates the Development of Dysplastic Mammary Lesions in Tumor-Prone Transgenic Mice. Mol. Biol. Cell 14: 1027-1042 [Abstract] [Full Text]  
  • Kietzmann, T., Samoylenko, A., Roth, U., Jungermann, K. (2003). Hypoxia-inducible factor-1 and hypoxia response elements mediate the induction of plasminogen activator inhibitor-1 gene expression by insulin in primary rat hepatocytes. Blood 101: 907-914 [Abstract] [Full Text]  
  • Skaletz-Rorowski, A., Lutchman, M., Kureishi, Y., Lefer, D. J., Faust, J. R., Walsh, K. (2003). HMG-CoA reductase inhibitors promote cholesterol-dependent Akt/PKB translocation to membrane domains in endothelial cells. Cardiovasc Res 57: 253-264 [Abstract] [Full Text]  
  • Razani, B., Woodman, S. E., Lisanti, M. P. (2002). Caveolae: From Cell Biology to Animal Physiology. Pharmacol. Rev. 54: 431-467 [Abstract] [Full Text]  
  • Volonte, D., Zhang, K., Lisanti, M. P., Galbiati, F. (2002). Expression of Caveolin-1 Induces Premature Cellular Senescence in Primary Cultures of Murine Fibroblasts. Stress-Induced Premature Senescence Upregulates the Expression of Endogenous Caveolin-1. Mol. Biol. Cell 13: 2502-2517 [Abstract] [Full Text]  
  • Grassme, H., Jendrossek, V., Bock, J., Riehle, A., Gulbins, E. (2002). Ceramide-Rich Membrane Rafts Mediate CD40 Clustering. J. Immunol. 168: 298-307 [Abstract] [Full Text]  
  • Park, D. S., Lee, H., Riedel, C., Hulit, J., Scherer, P. E., Pestell, R. G., Lisanti, M. P. (2001). Prolactin Negatively Regulates Caveolin-1 Gene Expression in the Mammary Gland during Lactation, via a Ras-dependent Mechanism. J. Biol. Chem. 276: 48389-48397 [Abstract] [Full Text]  
  • BIRBES, H., EL BAWAB, S., HANNUN, Y. A., OBEID, L. M. (2001). Selective hydrolysis of a mitochondrial pool of sphingomyelin induces apoptosis. FASEB J. 15: 2669-2679 [Abstract] [Full Text]  
  • Monick, M. M., Mallampalli, R. K., Carter, A. B., Flaherty, D. M., McCoy, D., Robeff, P. K., Peterson, M. W., Hunninghake, G. W. (2001). Ceramide Regulates Lipopolysaccharide-Induced Phosphatidylinositol 3-Kinase and Akt Activity in Human Alveolar Macrophages. J. Immunol. 167: 5977-5985 [Abstract] [Full Text]  
  • Teruel, T., Hernandez, R., Lorenzo, M. (2001). Ceramide Mediates Insulin Resistance by Tumor Necrosis Factor-{alpha} in Brown Adipocytes by Maintaining Akt in an Inactive Dephosphorylated State. Diabetes 50: 2563-2571 [Abstract] [Full Text]  
  • Wiechen, K., Diatchenko, L., Agoulnik, A., Scharff, K. M., Schober, H., Arlt, K., Zhumabayeva, B., Siebert, P. D., Dietel, M., Schafer, R., Sers, C. (2001). Caveolin-1 Is Down-Regulated in Human Ovarian Carcinoma and Acts as a Candidate Tumor Suppressor Gene. Am. J. Pathol. 159: 1635-1643 [Abstract] [Full Text]  
  • Galbiati, F., Volonte', D., Liu, J., Capozza, F., Frank, P. G., Zhu, L., Pestell, R. G., Lisanti, M. P. (2001). Caveolin-1 Expression Negatively Regulates Cell Cycle Progression by Inducing G0/G1 Arrest via a p53/p21WAF1/Cip1-dependent Mechanism. Mol. Biol. Cell 12: 2229-2244 [Abstract] [Full Text]  
  • Liu, J., Lee, P., Galbiati, F., Kitsis, R. N., Lisanti, M. P. (2001). Caveolin-1 expression sensitizes fibroblastic and epithelial cells to apoptotic stimulation. Am. J. Physiol. Cell Physiol. 280: C823-C835 [Abstract] [Full Text]  
  • Lozano, J., Menendez, S., Morales, A., Ehleiter, D., Liao, W.-C., Wagman, R., Haimovitz-Friedman, A., Fuks, Z., Kolesnick, R. (2001). Cell Autonomous Apoptosis Defects in Acid Sphingomyelinase Knockout Fibroblasts. J. Biol. Chem. 276: 442-448 [Abstract] [Full Text]  
  • Lu, M. L., Schneider, M. C., Zheng, Y., Zhang, X., Richie, J. P. (2001). Caveolin-1 Interacts with Androgen Receptor. A POSITIVE MODULATOR OF ANDROGEN RECEPTOR MEDIATED TRANSACTIVATION. J. Biol. Chem. 276: 13442-13451 [Abstract] [Full Text]  
  • Igarashi, J., Bernier, S. G., Michel, T. (2001). Sphingosine 1-Phosphate and Activation of Endothelial Nitric-oxide Synthase. DIFFERENTIAL REGULATION OF Akt AND MAP KINASE PATHWAYS BY EDG AND BRADYKININ RECEPTORS IN VASCULAR ENDOTHELIAL CELLS. J. Biol. Chem. 276: 12420-12426 [Abstract] [Full Text]  
  • Volonte, D., Galbiati, F., Pestell, R. G., Lisanti, M. P. (2001). Cellular Stress Induces the Tyrosine Phosphorylation of Caveolin-1 (Tyr14) via Activation of p38 Mitogen-activated Protein Kinase and c-Src kinase. EVIDENCE FOR CAVEOLAE, THE ACTIN CYTOSKELETON, AND FOCAL ADHESIONS AS MECHANICAL SENSORS OF OSMOTIC STRESS. J. Biol. Chem. 276: 8094-8103 [Abstract] [Full Text]  
  • Cremesti, A., Paris, F., Grassme, H., Holler, N., Tschopp, J., Fuks, Z., Gulbins, E., Kolesnick, R. (2001). Ceramide Enables Fas to Cap and Kill. J. Biol. Chem. 276: 23954-23961 [Abstract] [Full Text]  
  • Razani, B., Engelman, J. A., Wang, X. B., Schubert, W., Zhang, X. L., Marks, C. B., Macaluso, F., Russell, R. G., Li, M., Pestell, R. G., Di Vizio, D., Hou, H. Jr., Kneitz, B., Lagaud, G., Christ, G. J., Edelmann, W., Lisanti, M. P. (2001). Caveolin-1 Null Mice Are Viable but Show Evidence of Hyperproliferative and Vascular Abnormalities. J. Biol. Chem. 276: 38121-38138 [Abstract] [Full Text]  
  • Igarashi, J., Michel, T. (2001). Sphingosine 1-Phosphate and Isoform-specific Activation of Phosphoinositide 3-Kinase beta . EVIDENCE FOR DIVERGENCE AND CONVERGENCE OF RECEPTOR-REGULATED ENDOTHELIAL NITRIC-OXIDE SYNTHASE SIGNALING PATHWAYS. J. Biol. Chem. 276: 36281-36288 [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»