This Article
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 Auvinen, M.
Right arrow Articles by Holtta, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Auvinen, M.
Right arrow Articles by Holtta, E.

 Previous Article  |  Next Article 

Mol. Cell. Biol., Dec 1995, 6513-6525, Vol 15, No. 12
Copyright © 1995, American Society for Microbiology

Ornithine decarboxylase- and ras-induced cell transformations: reversal by protein tyrosine kinase inhibitors and role of pp130CAS

M Auvinen, A Paasinen-Sohns, H Hirai, LC Andersson and E Holtta
Department of Pathology, Haartman Institute, University of Helsinki, Finland.

We have found that overexpression of human ornithine decarboxylase (ODC) induces cell transformation in NIH 3T3 and Rat-1 cells (M. Auvinen, A. Paasinen, L. C. Andersson, and E. Holtta, Nature (London) 360:355-358, 1992). The ODC-transformed cells display increased levels of tyrosine phosphorylation, in particular of a cluster of 130-kDa proteins. Here we show that one of the proteins with enhanced levels of tyrosine phosphorylation in ODC-overexpressing cells is the previously described p130 substrate of pp60v-src, known to associate also with v- Crk and designated p130CAS. We also studied the role of protein tyrosine phosphorylation in the ODC-induced cell transformation by exposing the cells to herbimycin A, a potent inhibitor of Src-family kinases, and to other inhibitors of protein tyrosine kinases. Treatment with the inhibitors reversed the phenotype of ODC-transformed cells to normal, with an organized, filamentous actin cytoskeleton. Coincidentally, the tyrosine hyperphosphorylation of p130 was markedly reduced, while the level of activity of ODC remained highly elevated. A similar reduction in pp130 phosphorylation and reversion of morphology by herbimycin A were observed in v-src- and c-Ha-ras-transformed cells. In addition, we show that expression of antisense mRNA for p130CAS resulted in reversion of the transformed phenotype of all these cell lines. An increased level of tyrosine kinase activity, not caused by c- Src or c-Abl, was further detected in the cytoplasmic fraction of ODC- transformed cells. Preliminary characteristics of this kinase are shown. These data indicate that p130CAS is involved in cell transformation by ODC, c-ras, and v-src oncogenes, raise the intriguing possibility that p130CAS may be generally required for transformation, and imply that there is at least one protein tyrosine kinase downstream of ODC that is instrumental for cell transformation.


This article has been cited by other articles:

  • Smith, H. W., Marra, P., Marshall, C. J. (2008). uPAR promotes formation of the p130Cas-Crk complex to activate Rac through DOCK180. JCB 182: 777-790 [Abstract] [Full Text]  
  • Lim, Y., Han, I., Jeon, J., Park, H., Bahk, Y.-Y., Oh, E.-S. (2004). Phosphorylation of Focal Adhesion Kinase at Tyrosine 861 Is Crucial for Ras Transformation of Fibroblasts. J. Biol. Chem. 279: 29060-29065 [Abstract] [Full Text]  
  • Goldberg, G. S., Alexander, D. B., Pellicena, P., Zhang, Z.-Y., Tsuda, H., Miller, W. T. (2003). Src Phosphorylates Cas on Tyrosine 253 to Promote Migration of Transformed Cells. J. Biol. Chem. 278: 46533-46540 [Abstract] [Full Text]  
  • Fabian, C. J., Kimler, B. F., Brady, D. A., Mayo, M. S., Chang, C. H. J., Ferraro, J. A., Zalles, C. M., Stanton, A. L., Masood, S., Grizzle, W. E., Boyd, N. F., Arneson, D. W., Johnson, K. A. (2002). A Phase II Breast Cancer Chemoprevention Trial of Oral {alpha}-Difluoromethylornithine: Breast Tissue, Imaging, and Serum and Urine Biomarkers. Clin. Cancer Res. 8: 3105-3117 [Abstract] [Full Text]  
  • Schipper, R. G., Verhofstad, A. A.J. (2002). Distribution Patterns of Ornithine Decarboxylase in Cells and Tissues: Facts, Problems, and Postulates. J. Histochem. Cytochem. 50: 1143-1160 [Abstract] [Full Text]  
  • Huang, J., Hamasaki, H., Nakamoto, T., Honda, H., Hirai, H., Saito, M., Takato, T., Sakai, R. (2002). Differential Regulation of Cell Migration, Actin Stress Fiber Organization, and Cell Transformation by Functional Domains of Crk-associated Substrate. J. Biol. Chem. 277: 27265-27272 [Abstract] [Full Text]  
  • Ruest, P. J., Shin, N.-Y., Polte, T. R., Zhang, X., Hanks, S. K. (2001). Mechanisms of CAS Substrate Domain Tyrosine Phosphorylation by FAK and Src. Mol. Cell. Biol. 21: 7641-7652 [Abstract] [Full Text]  
  • Bachrach, U., Wang, Y.-C., Tabib, A. (2001). Polyamines: New Cues in Cellular Signal Transduction. Physiology 16: 106-109 [Abstract] [Full Text]  
  • Xing, L., Ge, C., Zeltser, R., Maskevitch, G., Mayer, B. J., Alexandropoulos, K. (2000). c-Src Signaling Induced by the Adapters Sin and Cas Is Mediated by Rap1 GTPase. Mol. Cell. Biol. 20: 7363-7377 [Abstract] [Full Text]  
  • Brinkman, A., van der Flier, S., Kok, E. M., Dorssers, L. C. J. (2000). BCAR1, a Human Homologue of the Adapter Protein p130Cas, and Antiestrogen Resistance in Breast Cancer Cells. JNCI J Natl Cancer Inst 92: 112-120 [Abstract] [Full Text]  
  • Pomidor, M. M., Cimildoro, R., Lazatin, B., Zheng, P., Gurr,·, J. A., Leigh, I. M., Jänne, O. A., Tuan, R. S., Hickok, N. J. (1999). Phosphorylated Human Keratinocyte Ornithine Decarboxylase Is Preferentially Associated with Insoluble Cellular Proteins. Mol. Biol. Cell 10: 4299-4310 [Abstract] [Full Text]  
  • Hakak, Y., Martin, G. S. (1999). Cas Mediates Transcriptional Activation of the Serum Response Element by Src. Mol. Cell. Biol. 19: 6953-6962 [Abstract] [Full Text]  
  • Zhang, Z., Hernandez-Lagunas, L., Horne, W. C., Baron, R. (1999). Cytoskeleton-dependent Tyrosine Phosphorylation of the p130Cas Family Member HEF1 Downstream of the G Protein-coupled Calcitonin Receptor. CALCITONIN INDUCES THE ASSOCIATION OF HEF1, PAXILLIN, AND FOCAL ADHESION KINASE. J. Biol. Chem. 274: 25093-25098 [Abstract] [Full Text]  
  • Kirsch, K. H., Georgescu, M.-M., Ishimaru, S., Hanafusa, H. (1999). CMS: An adapter molecule involved in cytoskeletal rearrangements. Proc. Natl. Acad. Sci. USA 96: 6211-6216 [Abstract] [Full Text]  
  • Garcia-Guzman, M., Dolfi, F., Russello, M., Vuori, K. (1999). Cell Adhesion Regulates the Interaction between the Docking Protein p130Cas and the 14-3-3 Proteins. J. Biol. Chem. 274: 5762-5768 [Abstract] [Full Text]  
  • Garton, A. J., Tonks, N. K. (1999). Regulation of Fibroblast Motility by the Protein Tyrosine Phosphatase PTP-PEST. J. Biol. Chem. 274: 3811-3818 [Abstract] [Full Text]  
  • Meksuriyen, D., Fukuchi-Shimogori, T., Tomitori, H., Kashiwagi, K., Toida, T., Imanari, T., Kawai, G., Igarashi, K. (1998). Formation of a Complex Containing ATP, Mg2+, and Spermine. STRUCTURAL EVIDENCE AND BIOLOGICAL SIGNIFICANCE. J. Biol. Chem. 273: 30939-30944 [Abstract] [Full Text]  
  • Chan, Y. R., Gallo, R. L. (1998). PR-39, a Syndecan-inducing Antimicrobial Peptide, Binds and Affects p130Cas. J. Biol. Chem. 273: 28978-28985 [Abstract] [Full Text]  
  • Casamassima, A., Rozengurt, E. (1998). Insulin-like Growth Factor I Stimulates Tyrosine Phosphorylation of p130Cas, Focal Adhesion Kinase, and Paxillin. ROLE OF PHOSPHATIDYLINOSITOL 3'-KINASE AND FORMATION OF A p130Cas·Crk COMPLEX. J. Biol. Chem. 273: 26149-26156 [Abstract] [Full Text]  
  • Cao, L., Zhang, L., Ruiz-Lozano, P., Yang, Q., Chien, K. R., Graham, R. M., Zhou, M. (1998). A Novel Putative Protein-tyrosine Phosphatase Contains a BRO1-like Domain and Suppresses Ha-ras-mediated Transformation. J. Biol. Chem. 273: 21077-21083 [Abstract] [Full Text]  
  • Needham, L. K., Rozengurt, E. (1998). Galpha 12 and Galpha 13 Stimulate Rho-dependent Tyrosine Phosphorylation of Focal Adhesion Kinase, Paxillin, and p130 Crk-associated Substrate. J. Biol. Chem. 273: 14626-14632 [Abstract] [Full Text]  
  • Law, S. F., Zhang, Y.-Z., Klein-Szanto, A. J. P., Golemis, E. A. (1998). Cell Cycle-Regulated Processing of HEF1 to Multiple Protein Forms Differentially Targeted to Multiple Subcellular Compartments. Mol. Cell. Biol. 18: 3540-3551 [Abstract] [Full Text]  
  • Takahashi, T., Kawahara, Y., Taniguchi, T., Yokoyama, M. (1998). Tyrosine phosphorylation and association of p130Cas and c-Crk II by ANG II in vascular smooth muscle cells. Am. J. Physiol. Heart Circ. Physiol. 274: H1059-H1065 [Abstract] [Full Text]  
  • Liu, F., Sells, M. A., Chernoff, J. (1998). Transformation Suppression by Protein Tyrosine Phosphatase 1B Requires a Functional SH3 Ligand. Mol. Cell. Biol. 18: 250-259 [Abstract] [Full Text]  
  • Segnitz, B., Gehring, U. (1997). The Function of Steroid Hormone Receptors Is Inhibited by the hsp90-specific Compound Geldanamycin. J. Biol. Chem. 272: 18694-18701 [Abstract] [Full Text]  
  • Nievers, M., Birge, R., Greulich, H, Verkleij, A., Hanafusa, H, van Bergen en Henegouwen, P. (1997). v-Crk-induced cell transformation: changes in focal adhesion composition and signaling. J. Cell Sci. 110: 389-399 [Abstract]  
  • Salgia, R., Pisick, E., Sattler, M., Li, J.-L., Uemura, N., Wong, W.-K., Burky, S. A., Hirai, H., Chen, L. B., Griffin, J. D. (1996). p130CAS Forms a Signaling Complex with the Adapter Protein CRKL in Hematopoietic Cells Transformed by the BCR/ABL Oncogene. J. Biol. Chem. 271: 25198-25203 [Abstract] [Full Text]  
  • Harte, M. T., Hildebrand, J. D., Burnham, M. R., Bouton, A. H., Parsons, J. T. (1996). p130Cas, a Substrate Associated with v-Src and v-Crk, Localizes to Focal Adhesions and Binds to Focal Adhesion Kinase. J. Biol. Chem. 271: 13649-13655 [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»