Protein kinase Cι: Human oncogene, prognostic marker and therapeutic target

Alan P. Fields, Roderick P. Regala

Research output: Contribution to journalReview articlepeer-review

103 Scopus citations


The protein kinase C (PKC) family of serine/threonine kinases has been the subject of intensive study in the field of cancer since their initial discovery as major cellular receptors for the tumor promoting phorbol esters nearly 30 years ago. However, despite these efforts, the search for a direct genetic link between members of the PKC family and human cancer has yielded only circumstantial evidence that any PKC isozyme is a true cancer gene. This situation changed in the past year with the discovery that atypical protein kinase C iota (PKCι) is a bonafide human oncogene. PKCι is required for the transformed growth of human cancer cells and the PKCι gene is the target of tumor-specific gene amplification in multiple forms of human cancer. PKCι participates in multiple aspects of the transformed phenotype of human cancer cells including transformed growth, invasion and survival. Herein, we review pertinent aspects of atypical PKC structure, function and regulation that relate to the role of these enzymes in oncogenesis. We discuss the evidence that PKCι is a human oncogene, review mechanisms controlling PKCι expression in human cancers, and describe the molecular details of PKCι-mediated oncogenic signaling. We conclude with a discussion of how oncogenic PKCι signaling has been successfully targeted to identify a novel, mechanism-based therapeutic drug currently entering clinical trials for treatment of human lung cancer. Throughout, we identify key unanswered questions and exciting future avenues of investigation regarding this important oncogenic molecule.

Original languageEnglish (US)
Pages (from-to)487-497
Number of pages11
JournalPharmacological Research
Issue number6
StatePublished - Jun 2007


  • Atypical protein kinase C
  • Aurothiomalate
  • Cancer signaling
  • Cell polarity
  • Hyperproliferation
  • Invasion and metastasis
  • Mechanism-based therapeutics
  • Par6
  • Phox/Bem1 domain

ASJC Scopus subject areas

  • Pharmacology


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