CDK8
Cyclin-dependent kinase 8 (EC 2.7.11.22) (EC 2.7.11.23) (Cell division protein kinase 8) (Mediator complex subunit CDK8) (Mediator of RNA polymerase II transcription subunit CDK8) (Protein kinase K35)
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Microarray gene expression data were used to analyze the expression pattern of cyclin, cyclin-dependent kinase (CDKs) and cyclin-dependent kinase inhibitor (CDKIs) genes from human pancreatic islets with and without type 2 diabetes (T2D). Of the cyclin genes, CCNI was the most expressed. Data obtained from microarray and qRT-PCR showed higher expression of CCND1 in diabetic islets. Among the CDKs, CDK4, CDK8 and CDK9 were highly expressed, while CDK1 was expressed at low level. High expression of [[CDK18]] was observed in diabetic islets. Of the CDKIs, CDKN1A expression was higher in diabetic islets in both microarray and qRT-PCR. Expression of CDKN1A, [[CDKN2A]], CCNI2, CDK3 and CDK16 was correlated with age. Finally, eight SNPs in these genes were associated with T2D in the DIAGRAM database. Our data provide a comprehensive expression pattern of cell cycle genes in human islets. More human studies are required to confirm and reproduce animal studies.
MeSH Terms
- Aged
- Aging
- Case-Control Studies
- Cells, Cultured
- Cyclin-Dependent Kinase Inhibitor Proteins
- Cyclin-Dependent Kinases
- Cyclins
- Diabetes Mellitus, Type 2
- Female
- Gene Expression Profiling
- Genes, cdc
- Genetic Association Studies
- Genetic Predisposition to Disease
- Humans
- Insulin
- Insulin Secretion
- Islets of Langerhans
- Male
- Middle Aged
- Oligonucleotide Array Sequence Analysis
- Polymorphism, Single Nucleotide
- Transcriptome
During early postnatal development, cardiomyocytes, which comprise about 80% of ventricular mass and volume, become phenotypically developed to facilitate their contractile functions and terminally differentiated to grow only in size but not in cell number. These changes are due to the expression of contractile proteins as well as the regulation of intracellular signal transduction proteins. In this study, the expression patterns of several protein kinases involved in various cardiac functions and cell-cycle control were analyzed by Western blotting of ventricular extracts from 1-, 10-, 20-, 50-, and 365-day-old rats. The expression level of cAMP-dependent protein kinase was slightly decreased (20%) over the first year, whereas no change was detected in cGMP-dependent protein kinase I. Calmodulin-dependent protein kinase II, which is involved in Ca2 uptake into the sarcoplasmic reticulum, was increased as much as ten-fold. To the contrary, the expressions of protein kinase C-alpha and iota declined 77% with age. Cyclin-dependent protein kinases (CDKs) such as CDK1, CDK2, CDK4, and CDK5, which are required for cell-cycle progression, abruptly declined to almost undetectable levels after 10-20 days of age. In contrast, other CDK-related kinases, such as CDK8 or Kkialre, did not change significantly or increased up to 50% with age, respectively. Protein kinases implicated in CDK regulation such as CDK7 and Wee1 were either slightly increased in expression or did not change significantly. All of the proteins that were detected in ventricular extracts were also identified in isolated cardiac myocytes in equivalent amounts and analyzed for their relative expression in ten other adult rat tissues.
MeSH Terms
- Aging
- Amino Acid Sequence
- Animals
- Blotting, Western
- Calcium-Calmodulin-Dependent Protein Kinase Type 2
- Calcium-Calmodulin-Dependent Protein Kinases
- Cell Cycle Proteins
- Cell Extracts
- Cyclic Nucleotide-Regulated Protein Kinases
- Cyclin-Dependent Kinases
- Heart Ventricles
- Male
- Molecular Sequence Data
- Myocardium
- Nuclear Proteins
- Organ Specificity
- Protein Kinase C
- Protein-Tyrosine Kinases
- Rats
- Rats, Sprague-Dawley
- Second Messenger Systems