Atypical Protein Kinase Cι as a human oncogene and therapeutic target

Peter J. Parker, Verline Justilien, Philippe Riou, Mark Linch, Alan P Fields

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Protein kinase inhibitors represent a major class of targeted therapeutics that has made a positive impact on treatment of cancer and other disease indications. Among the promising kinase targets for further therapeutic development are members of the Protein Kinase C (PKC) family. The PKCs are central components of many signaling pathways that regulate diverse cellular functions including proliferation, cell cycle, differentiation, survival, cell migration, and polarity. Genetic manipulation of individual PKC isozymes has demonstrated that they often fulfill distinct, nonredundant cellular functions. Participation of PKC members in different intracellular signaling pathways reflects responses to varying extracellular stimuli, intracellular localization, tissue distribution, phosphorylation status, and intermolecular interactions. PKC activity, localization, phosphorylation, and/or expression are often altered in human tumors, and PKC isozymes have been implicated in various aspects of transformation, including uncontrolled proliferation, migration, invasion, metastasis, angiogenesis, and resistance to apoptosis. Despite the strong relationship between PKC isozymes and cancer, to date only atypical PKCiota has been shown to function as a bona fide oncogene, and as such is a particularly attractive therapeutic target for cancer treatment. In this review, we discuss the role of PKCiota in transformation and describe mechanism-based approaches to therapeutically target oncogenic PKCiota signaling in cancer.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalBiochemical Pharmacology
Volume88
Issue number1
DOIs
StatePublished - Mar 1 2014

Fingerprint

Oncogenes
Protein Kinase C
Isoenzymes
Phosphorylation
Neoplasms
Therapeutics
Cell Polarity
Oncology
Cell proliferation
Tissue Distribution
Protein Kinase Inhibitors
Cell Movement
PKC-3 protein
Tumors
Cell Differentiation
Cell Cycle
Phosphotransferases
Tissue
Apoptosis
Neoplasm Metastasis

Keywords

  • Atypical Protein Kinase Cι
  • Cellular transformation
  • Mechanism-based therapeutics
  • Oncogenic signaling
  • Phox-Bem1 (PB1) domain

ASJC Scopus subject areas

  • Pharmacology
  • Biochemistry

Cite this

Atypical Protein Kinase Cι as a human oncogene and therapeutic target. / Parker, Peter J.; Justilien, Verline; Riou, Philippe; Linch, Mark; Fields, Alan P.

In: Biochemical Pharmacology, Vol. 88, No. 1, 01.03.2014, p. 1-11.

Research output: Contribution to journalArticle

Parker, Peter J. ; Justilien, Verline ; Riou, Philippe ; Linch, Mark ; Fields, Alan P. / Atypical Protein Kinase Cι as a human oncogene and therapeutic target. In: Biochemical Pharmacology. 2014 ; Vol. 88, No. 1. pp. 1-11.
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