Extracellular catalytic subunit activity of the cAMP-dependent protein kinase in prostate cancer
| Autor: | M E, Cvijic, T, Kita, W, Shih, R S, DiPaola, K V, Chin |
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| Rok vydání: | 2000 |
| Předmět: |
Adult
Male Blotting Western Cyclic AMP-Dependent Protein Kinase Type II CHO Cells Mice Catalytic Domain Cricetinae Biomarkers Tumor Cyclic AMP Tumor Cells Cultured Animals Humans Phosphorylation Aged Aged 80 and over Dose-Response Relationship Drug L-Lactate Dehydrogenase Intracellular Signaling Peptides and Proteins Prostatic Neoplasms Middle Aged Prostate-Specific Antigen Cyclic AMP-Dependent Protein Kinases Culture Media Case-Control Studies Female Carrier Proteins |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 6(6) |
| ISSN: | 1078-0432 |
| Popis: | The role of cAMP in cell growth and differentiation, gene expression, and neuronal function is mediated by the cAMP-dependent protein kinase (PKA). Differential expression of type I and type II PKA has been correlated with neoplastic transformation and differentiation, respectively. PKA is primarily an intracellular enzyme. However, it has been demonstrated that PKA may be associated with the plasma membrane and is exposed to the extracellular environment. Here we report the first evidence for the presence of a free extracellular kinase activity of PKA in the growth media of cultured prostate and other cancer cells, as well as in plasma samples from prostate cancer patients. This PKA activity is specific due to its phosphorylation of the PKA-specific substrate kemptide and its inhibition by the potent and specific PKA inhibitor PKI, but not by other protein kinase-inhibitory peptides. Intriguingly, this exoprotein kinase activity is cAMP independent, suggesting that only the catalytic subunit is secreted, and therefore the kinase activity is not modulated by the regulatory subunit of PKA. Western blot analysis of the culture supernatant from prostate cancer cells indicates the presence of the catalytic subunit. This increase in extracellular PKA catalytic subunit activity in prostate cancer may have profound effects on the tumorigenesis of prostate cancer and may serve as a novel marker and therapeutic target for the disease. |
| Databáze: | OpenAIRE |
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