Cardiovascular disorders

Ischemia; Rift Valley fever

Activation of PKCe has been demonstrated to be cardioprotective in animal models of myocardial ischemia and reperfusion injury, potentially suggesting a role for the PKCe protein in cellular anti-oxidant mechanisms. In addition, PKCe is hypothesized to interact with components of the mitochondrial transition pore, specifically Vdac, and mediate inhibition of Ca2+ induced pore opening. Loss-of-function mutations in this protein are linked with ischemia, presumably through the loss of the protective anti-oxidant function of the protein, leading to exaggerated oxidative tissue damage. Furthermore, mutations in the PKCe gene are linked to Rift Valley Fever, a viral infection transmitted by aedes mosquitoes, which has symptoms including vomiting blood, jaundice, bleeding from the nose or gums, menorrhagia, and bleeding from venepuncture sites.
 

TranscriptoNET (www.transcriptonet.ca) analysis with mRNA expression data retrieved from the National Center for Biotechnology Information's Gene Expression Omnibus (GEO) database, which was normalized against 60 abundantly and commonly found proteins, indicated altered expression for this protein kinase as shown here as the percent change from normal tissue controls (%CFC) as supported with the Student T-test in the following types of human cancers: Barrett's esophagus epithelial metaplasia (%CFC= -47, p<0.013); Bladder carcinomas (%CFC= -46, p<0.0002); and Brain oligodendrogliomas (%CFC= -96, p<0.068). The COSMIC website notes an up-regulated expression score for PKCe in diverse human cancers of 462, which is close to the average score of 462 for the human protein kinases. The down-regulated expression score of 17 for this protein kinase in human cancers was 0.3-fold of the average score of 60 for the human protein kinases.

Insertional mutagenesis studies in mice support a role for this protein kinase in mouse cancer oncogenesis.

Percent mutation rates per 100 amino acids length in human cancers: 0.07 % in 25409 diverse cancer specimens. This rate is only -8 % lower and is very similar to the average rate of 0.075 % calculated for human protein kinases in general.

Highest percent mutation rates per 100 amino acids length in human cancers: 0.39 % in 589 stomach cancers tested; 0.35 % in 1296 large intestine cancers tested; 0.25 % in 603 endometrium cancers tested; 0.13 % in 710 oesophagus cancers tested; 0.12 % in 1276 kidney cancers tested; 0.1 % in 1316 breast cancers tested; 0.09 % in 891 ovary cancers tested; 0.09 % in 864 skin cancers tested; 0.09 % in 1956 lung cancers tested; 0.06 % in 942 upper aerodigestive tract cancers tested; 0.06 % in 238 bone cancers tested; 0.05 % in 273 cervix cancers tested; 0.04 % in 382 soft tissue cancers tested; 0.02 % in 558 thyroid cancers tested; 0.02 % in 548 urinary tract cancers tested; 0.02 % in 2009 haematopoietic and lymphoid cancers tested; 0.01 % in 2103 central nervous system cancers tested; 0.01 % in 1512 liver cancers tested; 0.01 % in 1467 pancreas cancers tested.

Most frequent mutations with the number of reports indicated in brackets: R502* (3).

Only 3 deletions, no insertions, and no mutations are noted on the COSMIC website.