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): ä PMID26090489show 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.
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J+Immunol+Res 2015 ; 2015 (ä): ä
