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 Li, W.
Right arrow Articles by Wang, L.-H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Li, W.
Right arrow Articles by Wang, L.-H.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, October 1998, p. 5888-5898, Vol. 18, No. 10
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Protein Kinase C-delta Is an Important Signaling Molecule in Insulin-Like Growth Factor I Receptor-Mediated Cell Transformation

Weiqun Li,1,* Yi-Xing Jiang,2 Jiachang Zhang,1 Lilian Soon,1 Lawrence Flechner,1 Veena Kapoor,1 Jacalyn H. Pierce,1 and Lu-Hai Wang2

Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892,1 and Department of Microbiology, The Mount Sinai Medical Center, New York, New York 100292

Received 23 January 1998/Returned for modification 2 March 1998/Accepted 20 July 1998

To investigate the potential role of protein kinase C-delta (PKC-delta ) in insulin-like growth factor I receptor (IGF-IR)-mediated cell transformation, an oncogenic gag-IGF-IR beta -fusion receptor lacking the entire extracellular domain, which was designated NM1, and a full-length IGF-IR were coexpressed with either wild-type PKC-delta (PKC-delta WT) or an ATP-binding mutant of PKC-delta (PKC-delta K376R) in NIH 3T3 fibroblasts. While overexpression of PKC-delta WT did not affect NM1- and IGF-IR-induced focus and colony formation of NIH 3T3 cells, expression of PKC-delta K376R severely impaired these events. In contrast, NM1-mediated cell growth in monolayer was not affected by coexpressing PKC-delta K376R. PKC-delta WT and PKC-delta K376R were constitutively phosphorylated on a tyrosine residue(s) in the NM1- and IGF-IR-expressing cells and were associated with them in an IGF-I-independent manner. Activated IGF-IR was able to phosphorylate purified PKC-delta in vitro and stimulated its kinase activity. Furthermore, the level of endogenous PKC-delta protein was up-regulated through transcriptional activation in response to long-term IGF-IR activation. Taken together, our results demonstrate that PKC-delta plays an important role in IGF-IR-mediated cell transformation, probably via association of the receptor with PKC-delta and its activation through protein up-regulation and tyrosine phosphorylation. Competition with endogenous PKC-delta for NM1 and IGF-IR association by PKC-delta K376R is probably an important mechanism underlying the PKC-delta K376R-mediated inhibition of cell transformation by NM1 and IGF-IR.


* Corresponding author. Mailing address: Laboratory of Cellular and Molecular Biology, Building 37, Room 1E24, NCI, 9000 Rockville Pike, Bethesda, MD 20892. Phone: (301) 496-1347. Fax: (301) 496-8479. E-mail: Liwe{at}dc37a.nci.nih.gov.


Molecular and Cellular Biology, October 1998, p. 5888-5898, Vol. 18, No. 10
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.



This article has been cited by other articles:

  • Kwon, J., Stephan, S., Mukhopadhyay, A., Muders, M. H., Dutta, S. K., Lau, J. S., Mukhopadhyay, D. (2009). Insulin Receptor Substrate-2 Mediated Insulin-like Growth Factor-I Receptor Overexpression in Pancreatic Adenocarcinoma through Protein Kinase C{delta}. Cancer Res. 69: 1350-1357 [Abstract] [Full Text]  
  • Uekita, T., Jia, L., Narisawa-Saito, M., Yokota, J., Kiyono, T., Sakai, R. (2007). CUB Domain-Containing Protein 1 Is a Novel Regulator of Anoikis Resistance in Lung Adenocarcinoma. Mol. Cell. Biol. 27: 7649-7660 [Abstract] [Full Text]  
  • Xia, S., Forman, L. W., Faller, D. V. (2007). Protein Kinase C{delta} Is Required for Survival of Cells Expressing Activated p21RAS. J. Biol. Chem. 282: 13199-13210 [Abstract] [Full Text]  
  • Brandman, R., Disatnik, M.-H., Churchill, E., Mochly-Rosen, D. (2007). Peptides Derived from the C2 Domain of Protein Kinase C{epsilon} ({epsilon}PKC) Modulate {epsilon}PKC Activity and Identify Potential Protein-Protein Interaction Surfaces. J. Biol. Chem. 282: 4113-4123 [Abstract] [Full Text]  
  • Kheifets, V., Bright, R., Inagaki, K., Schechtman, D., Mochly-Rosen, D. (2006). Protein Kinase C {delta} ({delta}PKC)-Annexin V Interaction: A REQUIRED STEP IN {delta}PKC TRANSLOCATION AND FUNCTION. J. Biol. Chem. 281: 23218-23226 [Abstract] [Full Text]  
  • Fottner, C., Minnemann, T., Kalmbach, S., Weber, M. M (2006). Overexpression of the insulin-like growth factor I receptor in human pheochromocytomas.. J Mol Endocrinol 36: 279-287 [Abstract] [Full Text]  
  • Choi, S.-Y., Kim, M.-J., Kang, C.-M., Bae, S., Cho, C.-K., Soh, J.-W., Kim, J.-H., Kang, S., Chung, H. Y., Lee, Y.-S., Lee, S.-J. (2006). Activation of Bak and Bax through c-Abl-Protein Kinase C{delta}-p38 MAPK Signaling in Response to Ionizing Radiation in Human Non-small Cell Lung Cancer Cells. J. Biol. Chem. 281: 7049-7059 [Abstract] [Full Text]  
  • Tabata, C., Kubo, H., Tabata, R., Wada, M., Sakuma, K., Ichikawa, M., Fujita, S., Mio, T., Mishima, M. (2006). All-trans retinoic acid modulates radiation-induced proliferation of lung fibroblasts via IL-6/IL-6R system. Am. J. Physiol. Lung Cell. Mol. Physiol. 290: L597-L606 [Abstract] [Full Text]  
  • Ryer, E. J., Sakakibara, K., Wang, C., Sarkar, D., Fisher, P. B., Faries, P. L., Kent, K. C., Liu, B. (2005). Protein Kinase C Delta Induces Apoptosis of Vascular Smooth Muscle Cells through Induction of the Tumor Suppressor p53 by Both p38-dependent and p38-independent Mechanisms. J. Biol. Chem. 280: 35310-35317 [Abstract] [Full Text]  
  • Hurbin, A., Coll, J.-L., Dubrez-Daloz, L., Mari, B., Auberger, P., Brambilla, C., Favrot, M.-C. (2005). Cooperation of Amphiregulin and Insulin-like Growth Factor-1 Inhibits Bax- and Bad-mediated Apoptosis via a Protein Kinase C-dependent Pathway in Non-small Cell Lung Cancer Cells. J. Biol. Chem. 280: 19757-19767 [Abstract] [Full Text]  
  • Amos, S., Martin, P. M., Polar, G. A., Parsons, S. J., Hussaini, I. M. (2005). Phorbol 12-Myristate 13-Acetate Induces Epidermal Growth Factor Receptor Transactivation via Protein Kinase C{delta}/c-Src Pathways in Glioblastoma Cells. J. Biol. Chem. 280: 7729-7738 [Abstract] [Full Text]  
  • Jelacic, T., Linnekin, D. (2005). PKC{delta} plays opposite roles in growth mediated by wild-type Kit and an oncogenic Kit mutant. Blood 105: 1923-1929 [Abstract] [Full Text]  
  • Jones, H E, Goddard, L, Gee, J M W, Hiscox, S, Rubini, M, Barrow, D, Knowlden, J M, Williams, S, Wakeling, A E, Nicholson, R I (2004). Insulin-like growth factor-I receptor signalling and acquired resistance to gefitinib (ZD1839; Iressa) in human breast and prostate cancer cells. Endocr Relat Cancer 11: 793-814 [Abstract] [Full Text]  
  • JACKSON, D. N., FOSTER, D. A. (2004). The enigmatic protein kinase C{delta}: complex roles in cell proliferation and survival. FASEB J. 18: 627-636 [Abstract] [Full Text]  
  • Wang, Q., Wang, X., Evers, B. M. (2003). Induction of cIAP-2 in Human Colon Cancer Cells through PKC{delta}/NF-{kappa}B. J. Biol. Chem. 278: 51091-51099 [Abstract] [Full Text]  
  • Clark, A. S., West, K. A., Blumberg, P. M., Dennis, P. A. (2003). Altered Protein Kinase C (PKC) Isoforms in Non-Small Cell Lung Cancer Cells: PKC{delta} Promotes Cellular Survival and Chemotherapeutic Resistance. Cancer Res. 63: 780-786 [Abstract] [Full Text]  
  • Novotny-Diermayr, V., Zhang, T., Gu, L., Cao, X. (2002). Protein Kinase C delta Associates with the Interleukin-6 Receptor Subunit Glycoprotein (gp) 130 via Stat3 and Enhances Stat3-gp130 Interaction. J. Biol. Chem. 277: 49134-49142 [Abstract] [Full Text]  
  • Morrish, B. C., Rumsby, M. G. (2002). The 5' Untranslated Region of Protein Kinase C{delta} Directs Translation by an Internal Ribosome Entry Segment That Is Most Active in Densely Growing Cells and during Apoptosis. Mol. Cell. Biol. 22: 6089-6099 [Abstract] [Full Text]  
  • Hermanto, U., Zong, C. S., Li, W., Wang, L.-H. (2002). RACK1, an Insulin-Like Growth Factor I (IGF-I) Receptor-Interacting Protein, Modulates IGF-I-Dependent Integrin Signaling and Promotes Cell Spreading and Contact with Extracellular Matrix. Mol. Cell. Biol. 22: 2345-2365 [Abstract] [Full Text]  
  • Joseloff, E., Cataisson, C., Aamodt, H., Ocheni, H., Blumberg, P., Kraker, A. J., Yuspa, S. H. (2002). Src Family Kinases Phosphorylate Protein Kinase C delta on Tyrosine Residues and Modify the Neoplastic Phenotype of Skin Keratinocytes. J. Biol. Chem. 277: 12318-12323 [Abstract] [Full Text]  
  • Mandil, R., Ashkenazi, E., Blass, M., Kronfeld, I., Kazimirsky, G., Rosenthal, G., Umansky, F., Lorenzo, P. S., Blumberg, P. M., Brodie, C. (2001). Protein Kinase C{{alpha}} and Protein Kinase C{{delta}} Play Opposite Roles in the Proliferation and Apoptosis of Glioma Cells. Cancer Res. 61: 4612-4619 [Abstract] [Full Text]  
  • Datta, K., Sundberg, C., Karumanchi, S. A., Mukhopadhyay, D. (2001). The 104-123 Amino Acid Sequence of the {beta}-domain of von Hippel-Lindau Gene Product Is Sufficient to Inhibit Renal Tumor Growth and Invasion. Cancer Res. 61: 1768-1775 [Abstract] [Full Text]  
  • Hyun, T., Yam, A., Pece, S., Xie, X., Zhang, J., Miki, T., Gutkind, J. S., Li, W. (2000). Loss of PTEN expression leading to high Akt activation in human multiple myelomas. Blood 96: 3560-3568 [Abstract] [Full Text]  
  • von Wichert, G., Jehle, P. M., Hoeflich, A., Koschnick, S., Dralle, H., Wolf, E., Wiedenmann, B., Boehm, B. O., Adler, G., Seufferlein, T. (2000). Insulin-like Growth Factor-I Is an Autocrine Regulator of Chromogranin A Secretion and Growth in Human Neuroendocrine Tumor Cells. Cancer Res. 60: 4573-4581 [Abstract] [Full Text]  
  • Li, W., Hyun, T., Heller, M., Yam, A., Flechner, L., Pierce, J. H., Rudikoff, S. (2000). Activation of Insulin-like Growth Factor I Receptor Signaling Pathway Is Critical for Mouse Plasma Cell Tumor Growth. Cancer Res. 60: 3909-3915 [Abstract] [Full Text]  
  • Liu, Y., Witte, S., Liu, Y.-C., Doyle, M., Elly, C., Altman, A. (2000). Regulation of Protein Kinase Ctheta Function during T Cell Activation by Lck-mediated Tyrosine Phosphorylation. J. Biol. Chem. 275: 3603-3609 [Abstract] [Full Text]  
  • Hornia, A., Lu, Z., Sukezane, T., Zhong, M., Joseph, T., Frankel, P., Foster, D. A. (1999). Antagonistic Effects of Protein Kinase C alpha and delta on Both Transformation and Phospholipase D Activity Mediated by the Epidermal Growth Factor Receptor. Mol. Cell. Biol. 19: 7672-7680 [Abstract] [Full Text]  
  • Cheng, H.-L., Shy, M., Feldman, E. L. (1999). Regulation of Insulin-Like Growth Factor-Binding Protein-5 Expression during Schwann Cell Differentiation. Endocrinology 140: 4478-4485 [Abstract] [Full Text]  
  • Soon, L., Flechner, L., Gutkind, J. S., Wang, L.-H., Baserga, R., Pierce, J. H., Li, W. (1999). Insulin-Like Growth Factor I Synergizes with Interleukin 4 for Hematopoietic Cell Proliferation Independent of Insulin Receptor Substrate Expression. Mol. Cell. Biol. 19: 3816-3828 [Abstract] [Full Text]  
  • Kronfeld, I., Kazimirsky, G., Lorenzo, P. S., Garfield, S. H., Blumberg, P. M., Brodie, C. (2000). Phosphorylation of Protein Kinase Cdelta on Distinct Tyrosine Residues Regulates Specific Cellular Functions. J. Biol. Chem. 275: 35491-35498 [Abstract] [Full Text]  
  • Sachdev, P., Jiang, Y.-X., Li, W., Miki, T., Maruta, H., Nur-e-Kamal, M. S. A., Wang, L.-H. (2001). Differential Requirement for Rho Family GTPases in an Oncogenic Insulin-like Growth Factor-I Receptor-induced Cell Transformation. J. Biol. Chem. 276: 26461-26471 [Abstract] [Full Text]  
  • Yam, A., Hyun, T., Li, W. (2001). Characterization of Insulin-like Growth Factor I (IGF-I) Receptor Mutants for Their Effects on IGF-I- and Interleukin 4-mediated DNA Synthesis of 32D Cells. J. Biol. Chem. 276: 24409-24413 [Abstract] [Full Text]  
  • Datta, K., Nambudripad, R., Pal, S., Zhou, M., Cohen, H. T., Mukhopadhyay, D. (2000). Inhibition of Insulin-like Growth Factor-I-mediated Cell Signaling by the von Hippel-Lindau Gene Product in Renal Cancer. J. Biol. Chem. 275: 20700-20706 [Abstract] [Full Text]