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Trends in Cancer Research   Volumes    Volume 13 
Protein kinase C: Its role in RTK processing
Carol A. Heckman, J. Gordon Wade
Pages: 1 - 28
Number of pages: 28
Trends in Cancer Research
Volume 13 

Copyright © 2018 Research Trends. All rights reserved

Protein kinase C (PKC) affects signal transduction, vesicle trafficking, chemotactic activity, and cell polarity. It is the target of phorbol ester tumor promoters, but the phorbol esters have a variety of effects on cell growth – even opposite effects. Despite the importance of tumor promotion in cancer, and PKC in tumor promotion, it remains unknown how PKC affects signal transduction in a way that has major consequences for cancer development. PKC has a well-known role in downregulating or desensitizing receptors to further input at the earliest stages of signaling. The signalosomes assembled on receptor tyrosine kinases (RTKs) undergo progressive refinement, and there is some evidence suggesting PKC intervenes at these stages of signal processing. New light may be shed on the complexity of receptor processing by identifying signaling intermediates affected by PKC. It is possible to infer the composition of protein assemblies (signalosomes) on the epidermal growth factor receptor (EGFR) complex by integrating knowledge from proteomics studies with results from cell/molecular research. Although the full complexity of such complexes cannot be conveyed, the results allowed identification of inflection points where the signalosome composition is altered. Inflections can be anticipated due to Src and Cbl-mediated activities, as both are substrates of PKC and dock on the receptor. In this context, it is essential to develop analogies to convey the complexity of signaling downstream of receptor activation. We propose an analogy for temporal intervention in signalosome composition, similar to the concept of temporality of PKC-receptor interactions proposed by others. It likens PKC to service workers in the economy. To fulfill their roles, such workers, for example, caterers and taxi drivers, can be mobilized at different times and places. PKCs maintain a presence in the cytoplasm, and wherever and whenever they are needed, they are called up in numbers that have a relationship to the strength of the signaling input.
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