Protein kinase C isozymes as potential therapeutic targets in immune disorders.
BACKGROUND
Members of the protein kinase C (PKC) family are key signalling mediators in immune responses, and pharmacological inhibition of PKCs may be useful for treating immune-mediated diseases.


OBJECTIVE
To review and discuss the insights gained so far into various PKC isozymes and the therapeutic potential and challenges of developing PKC inhibitors for immune disorder therapy.


METHODS
A literature review of the role of PKCs in immune cell signalling and recent studies describing immune functions associated with PKC isozyme deficiency in relevant mouse disease models, followed by specific case studies of current and potential therapeutic strategies targeting PKCs.


CONCLUSIONS
There is vast amount of data supporting PKC isozymes as attractive drug targets for certain immune disorders. Although the development of specific PKC isozyme inhibitors has been challenging, some progress has been made. It remains to be seen if broad-scale or isozyme-selective inhibition of PKC will have clinical efficacy.
Lee
Matthew R
MR
Amgen, Inc., Molecular Structure, 1 Amgen Center Drive, Thousand Oaks, CA 91320, USA.
Duan
Wei
W
Tan
Seng-Lai
SL
D000818:Animals; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007154:Immune System Diseases / Q000188:drug therapy*; D007527:Isoenzymes; D051379:Mice; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D015398:Signal Transduction
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D011493:Protein Kinase C