Journal of Cancer Research and Clinical Oncology

, Volume 133, Issue 11, pp 793–808 | Cite as

Protein kinase C family: On the crossroads of cell signaling in skin and tumor epithelium

  • D. BreitkreutzEmail author
  • L. Braiman-Wiksman
  • N. Daum
  • M. F. Denning
  • T. Tennenbaum


The protein kinase C (PKC) family represents a large group of phospholipid dependent enzymes catalyzing the covalent transfer of phosphate from ATP to serine and threonine residues of proteins. Phosphorylation of the substrate proteins induces a conformational change resulting in modification of their functional properties. The PKC family consists of at least ten members, divided into three subgroups: classical PKCs (α, βI, βII, γ), novel PKCs (δ, ε, η, θ), and atypical PKCs (ζ, ι/λ). The specific cofactor requirements, tissue distribution, and cellular compartmentalization suggest differential functions and fine tuning of specific signaling cascades for each isoform. Thus, specific stimuli can lead to differential responses via isoform specific PKC signaling regulated by their expression, localization, and phosphorylation status in particular biological settings. PKC isoforms are activated by a variety of extracellular signals and, in turn, modify the activities of cellular proteins including receptors, enzymes, cytoskeletal proteins, and transcription factors. Accordingly, the PKC family plays a central role in cellular signal processing. Accumulating data suggest that various PKC isoforms participate in the regulation of cell proliferation, differentiation, survival and death. These findings have enabled identification of abnormalities in PKC isoform function, as they occur in several cancers. Specifically, the initiation of squamous cell carcinoma formation and progression to the malignant phenotype was found to be associated with distinct changes in PKC expression, activation, distribution, and phosphorylation. These studies were recently further extended to transgenic and knockout animals, which allowed a more direct analysis of individual PKC functions. Accordingly, this review is focused on the involvement of PKC in physiology and pathology of the skin.


Phorbol Ester Basal Cell Carcinoma Outer Root Sheath Cell Skin Tumor Promotion Spinous Marker 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • D. Breitkreutz
    • 1
    Email author
  • L. Braiman-Wiksman
    • 2
  • N. Daum
    • 1
  • M. F. Denning
    • 3
  • T. Tennenbaum
    • 4
  1. 1.Division of Differentiation and Carcinogenesis (A080/A110)German Cancer Research Center (DKFZ)HeidelbergGermany
  2. 2.HealOr LtdNess ZionaIsrael
  3. 3.Department of Pathology and Oncology InstituteLoyola University ChicagoMaywoodUSA
  4. 4.Faculty of Life SciencesBar-Ilan UniversityRamat-GanIsrael

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