Skip to main content
SpringerLink
Log in

PKC–PKD Interplay in Cancer

  • Chapter
  • First Online:
Protein Kinase C in Cancer Signaling and Therapy

Part of the book series: Current Cancer Research ((CUCR))

  • 695 Accesses

Abstract

The family of protein kinase D (PKD) serine/threonine kinases is a novel diacylglycerol (DAG) receptor and an immediate target of protein kinase C (PKC). The PKC/PKD pathway regulates many important biological processes in response to growth factor receptor and G-protein-coupled receptor activation. Recent studies have linked PKD to hyperproliferative disorders and cancer in several organs. Aberrant expression and activity of PKD have been demonstrated in malignant tumors and are associated with tumor progression. PKD has been implicated in neoplastic transformation and tumor metastasis by modulating tumor cell proliferation, survival, migration, invasion, and, potentially, angiogenesis. Important downstream targets of PKC/PKD in these processes have been identified. Furthermore, selective targeting of the PKC/PKD signaling in cancer is now possible with the discovery of potent and selective small molecule inhibitors of PKD. Thus, the PKC/PKD pathway may contribute to cancer development and represent an emerging target for cancer therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abbas, A., & Gupta, S. (2008). The role of histone deacetylases in prostate cancer. Epigenetics, 3, 300–309.

    Article  PubMed  Google Scholar 

  • Al-Janadi, A., Chandana, S. R., & Conley, B. A. (2008). Histone deacetylation: An attractive target for cancer therapy? Drugs in R&D, 9, 369–383.

    Article  CAS  Google Scholar 

  • Altschmied, J., & Haendeler, J. (2008). A new kid on the block: PKD1: A promising target for antiangiogenic therapy? Arteriosclerosis, Thrombosis, and Vascular Biology, 28, 1689–1690.

    Article  PubMed  CAS  Google Scholar 

  • Auer, A., von Blume, J., Sturany, S., von Wichert, G., Van Lint, J., Vandenheede, J., et al. (2005). Role of the regulatory domain of protein kinase D2 in phorbol ester binding, catalytic activity, and nucleocytoplasmic shuttling. Molecular Biology of the Cell, 16, 4375–4385.

    Article  PubMed  CAS  Google Scholar 

  • Avkiran, M., Rowland, A. J., Cuello, F., & Haworth, R. S. Ullrich (2008). Protein kinase d in the cardiovascular system: Emerging roles in health and disease. Circulation Research, 102, 157–163.

    Article  PubMed  CAS  Google Scholar 

  • Bagowski, C. P., Stein-Gerlach, M., Choidas, A., & Ullrich, A. (1999). Cell-type specific phosphorylation of threonines T654 and T669 by PKD defines the signal capacity of the EGF receptor. The EMBO Journal, 18, 5567–5576.

    Article  PubMed  CAS  Google Scholar 

  • Bell, R. M., & Burns, D. J. (1991). Lipid activation of protein kinase C. The Journal of Biological Chemistry, 266, 4661–4664.

    PubMed  CAS  Google Scholar 

  • Blumberg, P. M. (1988). Protein kinase C as the receptor for the phorbol ester tumor promoters: Sixth Rhoads memorial award lecture. Cancer Research, 48, 1–8.

    PubMed  CAS  Google Scholar 

  • Bollag, W. B., Dodd, M. E., & Shapiro, B. A. (2004). Protein kinase D and keratinocyte proliferation. Drug News & Perspectives, 17, 117–126.

    Article  CAS  Google Scholar 

  • Bossuyt, J., Helmstadter, K., Wu, X., Clements-Jewery, H., Haworth, R. S., Avkiran, M. et al. (2008). Ca2+/calmodulin-dependent protein kinase II{delta} and protein kinase D overexpression reinforce the histone deacetylase 5 redistribution in heart failure. Circulation Research, 102, 695–702.

    Article  PubMed  CAS  Google Scholar 

  • Bowden, E. T., Barth, M., Thomas, D., Glazer, R. I., & Mueller, S. C. (1999). An invasion-related complex of cortactin, paxillin and PKCmu associates with invadopodia at sites of extracellular matrix degradation. Oncogene, 18, 4440–4449.

    Article  PubMed  CAS  Google Scholar 

  • Brose, N., & Rosenmund, C. (2002). Move over protein kinase C, you’ve got company: Alternative cellular effectors of diacylglycerol and phorbol esters. Journal of Cell Science, 115, 4399–4411.

    Article  PubMed  CAS  Google Scholar 

  • Buder-Hoffmann, S. A., Shukla, A., Barrett, T. F., MacPherson, M. B., Lounsbury, K. M., & Mossman, B. T. (2009). A protein kinase Cdelta-dependent protein kinase D pathway modulates ERK1/2 and JNK1/2 phosphorylation and Bim-associated apoptosis by asbestos. American Journal of Pathology, 174, 449–459.

    Article  PubMed  CAS  Google Scholar 

  • Chen, J., Deng, F., Singh, S. V., & Wang, Q. J. (2008). Protein kinase D3 (PKD3) contributes to prostate cancer cell growth and survival through a PKCepsilon/PKD3 pathway downstream of Akt and ERK 1/2. Cancer Research, 68, 3844–3853.

    Article  PubMed  CAS  Google Scholar 

  • Chung, E. K., & Stadler, W. M. (2008). Vascular endothelial growth factor pathway – targeted therapy as initial systemic treatment of patients with renal cancer. Clinical Genitourinary Cancer, 6, s22–s28.

    Article  PubMed  CAS  Google Scholar 

  • Colon-Gonzalez, F., & Kazanietz, M. G. (2006). C1 domains exposed: From diacylglycerol binding to protein–protein interactions. Biochimica et Biophysica Acta, 1761, 827–837.

    Article  PubMed  CAS  Google Scholar 

  • Cowell, C. F., Yan, I. K., Eiseler, T., Leightner, A. C., Doppler, H., & Storz, P. (2009). Loss of cell-cell contacts induces NF-kappaB via RhoA-mediated activation of protein kinase D1. Journal of Cellular Biochemistry, 106(4), 714–728.

    Article  PubMed  CAS  Google Scholar 

  • Croft, D. R., Sahai, E., Mavria, G., Li, S., Tsai, J., Lee, W. M., et al. (2004). Conditional ROCK activation in vivo induces tumor cell dissemination and angiogenesis. Cancer Research, 64, 8994–9001.

    Article  PubMed  CAS  Google Scholar 

  • Davidson-Moncada, J. K., Lopez-Lluch, G., Segal, A. W., & Dekker, L. V. (2002). Involvement of protein kinase D in Fc gamma-receptor activation of the NADPH oxidase in neutrophils. Biochemical Journal, 363, 95–103.

    Article  PubMed  CAS  Google Scholar 

  • Diaz Anel, A. M., & Malhotra, V. (2005). PKCeta is required for beta1gamma2/beta3gamma2- and PKD-mediated transport to the cell surface and the organization of the Golgi apparatus. The Journal of Cell Biology, 169, 83–91.

    Article  PubMed  Google Scholar 

  • Eiseler, T., Doeppler, H., Yan, I. K., Goodison, S., & Storz, P. (2009). Protein Kinase D1 regulates MMP expression and inhibits breast cancer cell invasion. Breast Cancer Research, 11, R13.

    Article  PubMed  Google Scholar 

  • Endo, K., Oki, E., Biedermann, V., Kojima, H., Yoshida, K., Johannes, F. J., et al. (2000). Proteolytic cleavage and activation of protein kinase C [micro] by caspase-3 in the apoptotic response of cells to 1-beta -D-arabinofuranosylcytosine and other genotoxic agents. The Journal of Biological Chemistry, 275, 18476–18481.

    Article  PubMed  CAS  Google Scholar 

  • Fang, C. X., Yang, X., Sreejayan, N., & Ren, J. (2006). Acetaldehyde promotes rapamycin-dependent activation of p70(S6K) and glucose uptake despite inhibition of Akt and mTOR in dopaminergic SH-SY5Y human neuroblastoma cells. Exp Neurol, 203, 196–204.

    Google Scholar 

  • Ferrannini, E., Galvan, A. Q., Gastaldelli, A., Camastra, S., Sironi, A. M., Toschi, E., et al. (1999). Insulin: New roles for an ancient hormone. European Journal of Clinical Investigation, 29, 842–852.

    Article  PubMed  CAS  Google Scholar 

  • Fielitz, J., Kim, M. S., Shelton, J. M., Qi, X., Hill, J. A., Richardson, J. A., et al. (2008). Requirement of protein kinase D1 for pathological cardiac remodeling. Proceedings of the National Academy of Sciences of the United States of America, 105, 3059–3063.

    Article  PubMed  CAS  Google Scholar 

  • Griner, E. M., & Kazanietz, M. G. (2007). Protein kinase C and other diacylglycerol effectors in cancer. Nature Reviews Cancer, 7, 281–294.

    Article  PubMed  CAS  Google Scholar 

  • Gschwendt, M., Dieterich, S., Rennecke, J., Kittstein, W., Mueller, H. J., & Johannes, F. J. (1996). Inhibition of protein kinase C mu by various inhibitors. Differentiation from protein kinase c isoenzymes. FEBS Letters, 392, 77–80.

    Article  PubMed  CAS  Google Scholar 

  • Guha, S., Rey, O., & Rozengurt, E. (2002). Neurotensin induces protein kinase C-dependent protein kinase D activation and DNA synthesis in human pancreatic carcinoma cell line PANC-1. Cancer Research, 62, 1632–1640.

    PubMed  CAS  Google Scholar 

  • Ha, C. H., Jhun, B. S., Kao, H. Y., & Jin, Z. G. (2008). VEGF stimulates HDAC7 phosphorylation and cytoplasmic accumulation modulating matrix metalloproteinase expression and angiogenesis. Arteriosclerosis, Thrombosis, and Vascular Biology, 28, 1782–1788.

    Article  PubMed  CAS  Google Scholar 

  • Ha, C. H., Wang, W., Jhun, B. S., Wong, C., Hausser, A., Pfizenmaier, K., et al. (2008). Protein kinase D-dependent phosphorylation and nuclear export of histone deacetylase 5 mediates vascular endothelial growth factor-induced gene expression and angiogenesis. The Journal of Biological Chemistry, 283, 14590–14599.

    Article  PubMed  CAS  Google Scholar 

  • Harrison, B. C., Kim, M. S., van Rooij, E., Plato, C. F., Papst, P. J., Vega, R. B., et al. (2006). Regulation of cardiac stress signaling by protein kinase d1. Molecular and Cellular Biology, 26, 3875–3888.

    Article  PubMed  CAS  Google Scholar 

  • Hausser, A., Storz, P., Hubner, S., Braendlin, I., Martinez-Moya, M., Link, G., et al. (2001). Protein kinase C mu selectively activates the mitogen-activated protein kinase (MAPK) p42 pathway. FEBS Letters, 492, 39–44.

    Article  PubMed  CAS  Google Scholar 

  • Hausser, A., Storz, P., Martens, S., Link, G., Toker, A., & Pfizenmaier, K. (2005). Protein kinase D regulates vesicular transport by phosphorylating and activating phosphatidylinositol-4 kinase IIIbeta at the Golgi complex. Nature Cell Biology, 7, 880–886.

    Article  PubMed  CAS  Google Scholar 

  • Hayashi, A., Seki, N., Hattori, A., Kozuma, S., & Saito, T. (1999). PKCnu, a new member of the protein kinase C family, composes a fourth subfamily with PKCmu. Biochimica et Biophysica Acta, 1450, 99–106.

    Article  PubMed  CAS  Google Scholar 

  • Hurd, C., & Rozengurt, E. (2001). Protein kinase D is sufficient to suppress EGF-induced c-Jun Ser 63 phosphorylation. Biochemical and Biophysical Research Communications, 282, 404–408.

    Article  PubMed  CAS  Google Scholar 

  • Hurd, C., Waldron, R. T., & Rozengurt, E. (2002). Protein kinase D complexes with C-Jun N-terminal kinase via activation loop phosphorylation and phosphorylates the C-Jun N-terminus. Oncogene, 21, 2154–2160.

    Article  PubMed  CAS  Google Scholar 

  • Iglesias, T., & Rozengurt, E. (1998). Protein kinase D activation by mutations within its pleckstrin homology domain. The Journal of Biological Chemistry, 273, 410–416.

    Article  PubMed  CAS  Google Scholar 

  • Jackson, L. N., Li, J., Chen, L. A., Townsend, C. M., & Evers, B. M. (2006). Overexpression of wild-type PKD2 leads to increased proliferation and invasion of BON endocrine cells. Biochemical and Biophysical Research Communications, 348, 945–949.

    Article  PubMed  CAS  Google Scholar 

  • Jaggi, M., Rao, P. S., Smith, D. J., Hemstreet, G. P., & Balaji, K. C. (2003). Protein kinase C mu is down-regulated in androgen-independent prostate cancer. Biochemical and Biophysical Research Communications, 307, 254–260.

    Article  PubMed  CAS  Google Scholar 

  • Jaggi, M., Rao, P. S., Smith, D. J., Wheelock, M. J., Johnson, K. R., Hemstreet, G. P., et al. (2005). E-cadherin phosphorylation by protein kinase D1/protein kinase C{mu} is associated with altered cellular aggregation and motility in prostate cancer. Cancer Research, 65, 483–492.

    PubMed  CAS  Google Scholar 

  • Jamora, C., Yamanouye, N., Van Lint, J., Laudenslager, J., Vandenheede, J. R., Faulkner, D. J., et al. (1999). Gbetagamma-mediated regulation of Golgi organization is through the direct activation of protein kinase D. Cell, 98, 59–68.

    Article  PubMed  CAS  Google Scholar 

  • Johannes, F. J., Horn, J., Link, G., Haas, E., Siemienski, K., Wajant, H., et al. (1998). Protein kinase Cmu downregulation of tumor-necrosis-factor-induced apoptosis correlates with enhanced expression of nuclear-factor-kappaB-dependent protective genes. European Journal of Biochemistry, 257, 47–54.

    Article  PubMed  CAS  Google Scholar 

  • Johannes, F. J., Prestle, J., Dieterich, S., Oberhagemann, P., Link, G., & Pfizenmaier, K. (1995). Characterization of activators and inhibitors of protein kinase C mu. European Journal of Biochemistry, 227, 303–307.

    Article  PubMed  CAS  Google Scholar 

  • Johannes, F. J., Prestle, J., Eis, S., Oberhagemann, P., & Pfizenmaier, K. (1994). PKCu is a novel, atypical member of the protein kinase C family. The Journal of Biological Chemistry, 269, 6140–6148.

    PubMed  CAS  Google Scholar 

  • Kim, M., Jang, H. R., Kim, J. H., Noh, S. M., Song, K. S., Cho, J. S., et al. (2008). Epigenetic inactivation of protein kinase D1 in gastric cancer and its role in gastric cancer cell migration and invasion. Carcinogenesis, 29, 629–637.

    Article  PubMed  CAS  Google Scholar 

  • Lambeth, J. D. (2007). Nox enzymes, ROS, and chronic disease: An example of antagonistic pleiotropy. Free Radical Biology and Medicine, 43, 332–347.

    Article  PubMed  CAS  Google Scholar 

  • Liljedahl, M., Maeda, Y., Colanzi, A., Ayala, I., Van Lint, J., & Malhotra, V. (2001). Protein kinase D regulates the fission of cell surface destined transport carriers from the trans-Golgi network. Cell, 104, 409–420.

    Article  PubMed  CAS  Google Scholar 

  • Liu, D., Evans, I., Britton, G., & Zachary, I. (2008). The zinc-finger transcription factor, early growth response 3, mediates VEGF-induced angiogenesis. Oncogene, 27, 2989–2998.

    Article  PubMed  CAS  Google Scholar 

  • Manning, G., Whyte, D. B., Martinez, R., Hunter, T., & Sudarsanam, S. (2002). The protein kinase complement of the human genome. Science, 298, 1912–1934.

    Article  PubMed  CAS  Google Scholar 

  • Martiny-Baron, G., Kazanietz, M. G., Mischak, H., Blumberg, P. M., Kochs, G., Hug, H., et al. (1993). Selective inhibition of protein kinase C isozymes by the indolocarbazole Go 6976. The Journal of Biological Chemistry, 268, 9194–9197.

    PubMed  CAS  Google Scholar 

  • Medeiros, R. B., Dickey, D. M., Chung, H., Quale, A. C., Nagarajan, L. R., Billadeau, D. D., et al. (2005). Protein kinase D1 and the beta 1 integrin cytoplasmic domain control beta 1 integrin function via regulation of Rap1 activation. Immunity, 23, 213–226.

    Article  PubMed  CAS  Google Scholar 

  • Nishizuka, Y. (1992). Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C. Science, 258, 607–614.

    Article  PubMed  CAS  Google Scholar 

  • Paolucci, L., & Rozengurt, E. (1999). Protein kinase D in small cell lung cancer cells: Rapid activation through protein kinase C. Cancer Research, 59, 572–577.

    PubMed  CAS  Google Scholar 

  • Paolucci, L., Sinnett-Smith, J., & Rozengurt, E. (2000). Lysophosphatidic acid rapidly induces protein kinase D activation through a pertussis toxin-sensitive pathway. American Journal of Physiology. Cell physiology, 278, C33–C39.

    PubMed  CAS  Google Scholar 

  • Prigozhina, N. L., & Waterman-Storer, C. M. (2004). Protein kinase D-mediated anterograde membrane trafficking is required for fibroblast motility. Current Biology, 14, 88–98.

    Article  PubMed  CAS  Google Scholar 

  • Rennecke, J., Rehberger, P. A., Furstenberger, G., Johannes, F. J., Stohr, M., Marks, F., et al. (1999). Protein-kinase-Cmu expression correlates with enhanced keratinocyte proliferation in normal and neoplastic mouse epidermis and in cell culture. International Journal of Cancer, 80, 98–103.

    Article  CAS  Google Scholar 

  • Rey, O., Yuan, J., Young, S. H., & Rozengurt, E. (2003). Protein kinase C nu/protein kinase D3 nuclear localization, catalytic activation, and intracellular redistribution in response to G protein-coupled receptor agonists. The Journal of Biological Chemistry, 278, 23773–23785.

    Article  PubMed  CAS  Google Scholar 

  • Rey, O., Zhukova, E., Sinnett-Smith, J., & Rozengurt, E. (2003). Vasopressin-induced intracellular redistribution of protein kinase D in intestinal epithelial cells. Journal of Cellular Physiology, 196, 483–492.

    Article  PubMed  CAS  Google Scholar 

  • Ristich, V. L., Bowman, P. H., Dodd, M. E., & Bollag, W. B. (2006). Protein kinase D distribution in normal human epidermis, basal cell carcinoma and psoriasis. British Journal of Dermatology, 154, 586–593.

    Article  PubMed  CAS  Google Scholar 

  • Rozengurt, E., Rey, O., & Waldron, R. T. (2005). Protein kinase D signaling. The Journal of Biological Chemistry, 280, 13205–13208.

    Article  PubMed  CAS  Google Scholar 

  • Sahai, E., & Marshall, C. J. (2003). Differing modes of tumour cell invasion have distinct requirements for Rho/ROCK signalling and extracellular proteolysis. Nature Cell Biology, 5, 711–719.

    Article  PubMed  CAS  Google Scholar 

  • Seufferlein, T. (2002). Novel protein kinases in pancreatic cell growth and cancer. International Journal of Gastrointestinal Cancer, 31, 15–21.

    Article  PubMed  CAS  Google Scholar 

  • Sharlow, E. R., Giridhar, K. V., Lavalle, C. R., Chen, J., Leimgruber, S., Barrett, R., et al. (2008). Potent and selective disruption of protein kinase d functionality by a benzoxoloazepinolone. The Journal of Biological Chemistry, 283, 33516–33526.

    Article  PubMed  CAS  Google Scholar 

  • Sinnett-Smith, J., Zhukova, E., Hsieh, N., Jiang, X., & Rozengurt, E. (2004). Protein kinase D potentiates DNA synthesis induced by Gq-coupled receptors by increasing the duration of ERK signaling in swiss 3T3 cells. The Journal of Biological Chemistry, 279, 16883–16893.

    Article  PubMed  CAS  Google Scholar 

  • Sinnett-Smith, J., Zhukova, E., Rey, O., & Rozengurt, E. (2007). Protein kinase D2 potentiates MEK/ERK/RSK signaling, c-Fos accumulation and DNA synthesis induced by bombesin in Swiss 3T3 cells. Journal of Cellular Physiology, 211, 781–790.

    Article  PubMed  CAS  Google Scholar 

  • Song, J., Li, J., Qiao, J., Jain, S., Mark Evers, B., & Chung, D. H. (2009). PKD prevents H2O2-induced apoptosis via NF-kappaB and p38 MAPK in RIE-1 cells. Biochemical and Biophysical Research Communications, 378, 610–614.

    Article  PubMed  CAS  Google Scholar 

  • Storz, P., Doppler, H., Johannes, F. J., & Toker, A. (2003). Tyrosine phosphorylation of protein kinase D in the pleckstrin homology domain leads to activation. The Journal of Biological Chemistry, 278, 17969–17976.

    Article  PubMed  CAS  Google Scholar 

  • Storz, P., Doppler, H., & Toker, A. (2004). Protein kinase Cdelta selectively regulates protein kinase D-dependent activation of NF-kappaB in oxidative stress signaling. Molecular and Cellular Biology, 24, 2614–2626.

    Article  PubMed  CAS  Google Scholar 

  • Storz, P., Doppler, H., & Toker, A. (2005). Protein kinase D mediates mitochondrion-to-nucleus signaling and detoxification from mitochondrial reactive oxygen species. Molecular and Cellular Biology, 25, 8520–8530.

    Article  PubMed  CAS  Google Scholar 

  • Storz, P., & Toker, A. (2003a). NF-kappaB signaling – an alternate pathway for oxidative stress responses. Cell Cycle, 2, 9–10.

    Article  PubMed  CAS  Google Scholar 

  • Storz, P., & Toker, A. (2003b). Protein kinase D mediates a stress-induced NF-kappaB activation and survival pathway. The EMBO Journal, 22, 109–120.

    Article  PubMed  CAS  Google Scholar 

  • Sturany, S., Van Lint, J., Muller, F., Wilda, M., Hameister, H., Hocker, M., et al. (2001). Molecular cloning and characterization of the human protein kinase D2. A novel member of the protein kinase D family of serine threonine kinases. The Journal of Biological Chemistry, 276, 3310–3318.

    Article  PubMed  CAS  Google Scholar 

  • Tan, M., Xu, X., Ohba, M., Ogawa, W., & Cui, M. Z. (2003). Thrombin rapidly induces protein kinase D phosphorylation, and protein kinase C delta mediates the activation. The Journal of Biological Chemistry, 278, 2824–2828.

    Article  PubMed  CAS  Google Scholar 

  • Tan, M., Xu, X., Ohba, M., Ogawa, W., & Cui, M. Z. (2004). Angiotensin II-induced protein kinase D activation is regulated by protein kinase Cdelta and mediated via the angiotensin II type 1 receptor in vascular smooth muscle cells. Arteriosclerosis, Thrombosis, and Vascular Biology, 24, 2271–2276.

    Article  PubMed  CAS  Google Scholar 

  • Trauzold, A., Schmiedel, S., Sipos, B., Wermann, H., Westphal, S., Roder, C., et al. (2003). PKCmu prevents CD95-mediated apoptosis and enhances proliferation in pancreatic tumour cells. Oncogene, 22, 8939–8947.

    Article  PubMed  CAS  Google Scholar 

  • Valverde, A. M., Sinnett-Smith, J., Van Lint, J., & Rozengurt, E. (1994). Molecular cloning and characterization of protein kinase D: A target for diacylglycerol and phorbol esters with a distinctive catalytic domain. Proceedings of the National Academy of Sciences of the United States of America, 91, 8572–8576.

    Article  PubMed  CAS  Google Scholar 

  • Van Lint, J., Ni, Y., Valius, M., Merlevede, W., & Vandenheede, J. R. (1998). Platelet-derived growth factor stimulates protein kinase D through the activation of phospholipase Cgamma and protein kinase C. The Journal of Biological Chemistry, 273, 7038–7043.

    Article  PubMed  Google Scholar 

  • Van Lint, J. V., Sinnett-Smith, J., & Rozengurt, E. (1995). Expression and characterization of PKD, a phorbol ester and diacylglycerol-stimulated serine protein kinase. The Journal of Biological Chemistry, 270, 1455–1461.

    Article  PubMed  Google Scholar 

  • Vantus, T., Vertommen, D., Saelens, X., Rykx, A., De Kimpe, L., Vancauwenbergh, S., et al. (2004). Doxorubicin-induced activation of protein kinase D1 through caspase-mediated proteolytic cleavage: Identification of two cleavage sites by microsequencing. Cellular Signalling, 16, 703–709.

    Article  PubMed  CAS  Google Scholar 

  • Vega, R. B., Harrison, B. C., Meadows, E., Roberts, C. R., Papst, P. J., Olson, E. N., et al. (2004). Protein kinases C and D mediate agonist-dependent cardiac hypertrophy through nuclear export of histone deacetylase 5. Molecular and Cellular Biology, 24, 8374–8385.

    Article  PubMed  CAS  Google Scholar 

  • Waldron, R. T., & Rozengurt, E. (2000). Oxidative stress induces protein kinase D activation in intact cells. Involvement of Src and dependence on protein kinase C. The Journal of Biological Chemistry, 275, 17114–17121.

    Article  PubMed  CAS  Google Scholar 

  • Waldron, R. T., & Rozengurt, E. (2003). Protein kinase C phosphorylates protein kinase D activation loop Ser744 and Ser748 and releases autoinhibition by the pleckstrin homology domain. The Journal of Biological Chemistry, 278, 154–163.

    Article  PubMed  CAS  Google Scholar 

  • Waldron, R. T., Whitelegge, J. P., Faull, K. F., & Rozengurt, E. (2007). Identification of a novel phosphorylation site in c-jun directly targeted in vitro by protein kinase D. Biochemical and Biophysical Research Communications, 356, 361–367.

    Article  PubMed  CAS  Google Scholar 

  • Wang, Q. J. (2006). PKD at the crossroads of DAG and PKC signaling. Trends in Pharmacological Sciences, 27, 317–323.

    Article  PubMed  CAS  Google Scholar 

  • Wang, Y., Schattenberg, J. M., Rigoli, R. M., Storz, P., & Czaja, M. J. (2004). Hepatocyte resistance to oxidative stress is dependent on protein kinase C-mediated down-regulation of c-Jun/AP-1. The Journal of Biological Chemistry, 279, 31089–31097.

    Article  PubMed  CAS  Google Scholar 

  • Wang, Y., Waldron, R. T., Dhaka, A., Patel, A., Riley, M. M., Rozengurt, E., et al. (2002). The RAS effector RIN1 directly competes with RAF and is regulated by 14-3-3 proteins. Molecular and Cellular Biology, 22, 916–926.

    Article  PubMed  CAS  Google Scholar 

  • Weinstein, I. B. (2002). Cancer. Addiction to oncogenes – the Achilles heal of cancer. Science, 297, 63–64.

    Article  PubMed  CAS  Google Scholar 

  • White, D. P., Caswell, P. T., & Norman, J. C. (2007). alpha v beta3 and alpha5beta1 integrin recycling pathways dictate downstream Rho kinase signaling to regulate persistent cell migration. The Journal of Cell Biology, 177, 515–525.

    Article  PubMed  CAS  Google Scholar 

  • Wong, C., & Jin, Z. G. (2005). Protein kinase C-dependent protein kinase D activation modulates ERK signal pathway and endothelial cell proliferation by vascular endothelial growth factor. The Journal of Biological Chemistry, 280, 33262–33269.

    Article  PubMed  CAS  Google Scholar 

  • Woods, A. J., White, D. P., Caswell, P. T., & Norman, J. C. (2004). PKD1/PKCmu promotes alphavbeta3 integrin recycling and delivery to nascent focal adhesions. The EMBO Journal, 23, 2531–2543.

    Article  PubMed  CAS  Google Scholar 

  • Yang, C., & Kazanietz, M. G. (2003). Divergence and complexities in DAG signaling: Looking beyond PKC. Trends in Pharmacological Sciences, 24, 602–608.

    Article  PubMed  CAS  Google Scholar 

  • Yeaman, C., Ayala, M. I., Wright, J. R., Bard, F., Bossard, C., Ang, A., et al. (2004). Protein kinase D regulates basolateral membrane protein exit from trans-Golgi network. Nature Cell Biology, 6, 106–112.

    Article  PubMed  CAS  Google Scholar 

  • Zhukova, E., Sinnett-Smith, J., & Rozengurt, E. (2001). Protein kinase D potentiates DNA synthesis and cell proliferation induced by bombesin, vasopressin, or phorbol esters in Swiss 3T3 cells. The Journal of Biological Chemistry, 276, 40298–40305.

    PubMed  CAS  Google Scholar 

  • Zugaza, J. L., Sinnett-Smith, J., Van Lint, J., & Rozengurt, E. (1996). Protein kinase D (PKD) activation in intact cells through a protein kinase C-dependent signal transduction pathway. The EMBO Journal, 15, 6220–6230.

    PubMed  Google Scholar 

  • Zugaza, J. L., Waldron, R. T., Sinnett-Smith, J., & Rozengurt, E. (1997). Bombesin, vasopressin, endothelin, bradykinin, and platelet-derived growth factor rapidly activate protein kinase D through a protein kinase C-dependent signal transduction pathway. The Journal of Biological Chemistry, 272, 23952–23960.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Work in our laboratory is supported by grants from the National Institutes of Health.

Author information

Authors and Affiliations

  1. Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, E1354 BST, Pittsburgh, PA, 15261, USA

    Q. Jane Wang

Authors
  1. Q. Jane Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Q. Jane Wang .

Editor information

Editors and Affiliations

  1. School of Medicine, University of Pennsylvania, Curie Boulevard 421, Philadeliphia, 19147, USA

    Marcelo G. Kazanietz

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Wang, Q.J. (2010). PKC–PKD Interplay in Cancer. In: Kazanietz, M. (eds) Protein Kinase C in Cancer Signaling and Therapy. Current Cancer Research. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-543-9_14

Download citation

  • DOI: https://doi.org/10.1007/978-1-60761-543-9_14

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60761-542-2

  • Online ISBN: 978-1-60761-543-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation