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Cell Signaling & Molecular Targets in Cancer pp 245–271Cite as

Protein Kinase D Signaling in Cancer

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Abstract

Protein Kinase D is a serine/threonine kinase that shows responsiveness to phorbol esters and diacylglycerol and is a direct target for Src family kinases, RhoGTPases and protein kinase C. Thus PKD on first view represents a bona fide oncogene and is currently investigated for its potential as a drug target for multiple cancers. This is supported by the discovery that PKD promotes tumor cell survival in response to damaging stresses such as increases in reactive oxygen species, but also enhances cell proliferation and DNA synthesis in response to activation by growth factor and G-protein-coupled receptors. Based on these findings, the development of PKD inhibitors is progressed within the field. However, accumulating reports also suggest that PKD activation suppresses directed cell migration and invasion, suggesting that PKD expression may be needed for early tumorigenic events, but is downregulated during metastatic progression. This chapter describes the known roles of PKD isoenzymes in all aspects of tumor biology as well as the signaling mechanisms they use, and discusses their potential value as drug targets in cancer.

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Acknowledgments

Research in the Storz laboratory is supported by grants from the Mayo Clinic SPORE for Pancreatic Cancer (P50 CA102701), the Mayo Clinic Breast Cancer SPORE (CA116201-03DR4), the NIH (GM86435 and CA135102), as well as a Bankhead–Coley grant (10BG11) from the Florida Department of Health.

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  1. Department for Cancer Biology, Mayo Clinic, Jacksonville, FL, 32224, USA

    Peter Storz Ph.D.

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    Malay Chatterjee

  2. , Division of Biochemistry & Chemistry, City University of New York Medical Scho, New York, 10031, New York, USA

    Khosrow Kashfi

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Storz, P. (2012). Protein Kinase D Signaling in Cancer. In: Chatterjee, M., Kashfi, K. (eds) Cell Signaling & Molecular Targets in Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-0730-0_11

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