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2015 ; 2015
(ä): 348798
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The Novel PKC? from Benchtop to Clinic
#MMPMID26090489
Hage-Sleiman R
; Hamze AB
; Reslan L
; Kobeissy H
; Dbaibo G
J Immunol Res
2015[]; 2015
(ä): 348798
PMID26090489
show ga
The protein kinases C (PKCs) are a family of serine/threonine kinases involved in
regulating multiple essential cellular processes such as survival, proliferation,
and differentiation. Of particular interest is the novel, calcium-independent
PKC? which plays a central role in immune responses. PKC? shares structural
similarities with other PKC family members, mainly consisting of an N-terminal
regulatory domain and a C-terminal catalytic domain tethered by a hinge region.
This isozyme, however, is unique in that it translocates to the immunological
synapse between a T cell and an antigen-presenting cell (APC) upon T cell
receptor-peptide MHC recognition. Thereafter, PKC? interacts physically and
functionally with downstream effectors to mediate T cell activation and
differentiation, subsequently leading to inflammation. PKC?-specific
perturbations have been identified in several diseases, most notably autoimmune
disorders, and hence the modulation of its activity presents an attractive
therapeutic intervention. To that end, many inhibitors of PKCs and PKC? have been
developed and tested in preclinical and clinical studies. And although
selectivity remains a challenge, results are promising for the future development
of effective PKC? inhibitors that would greatly advance the treatment of several
T-cell mediated diseases.