casein-kinase-ii and Nervous-System-Diseases

Protein kinase CK2 (formerly referred to as casein kinase II) is an evolutionary conserved, ubiquitous protein kinase. There are two paralog catalytic subunits, i.e. alpha (A1) and alpha' (A2). The alpha and alpha' subunits are linked to two beta subunits to produce a heterotetrameric structure. The catalytic alpha subunits are distantly related to the CMGC subfamily of kinases, such as the Cdk kinases. There are some peculiarities associated with protein kinase CK2, which are not found with most other protein kinases: (i) the enzyme is constitutively active, (ii) it can use ATP and GTP and (iii) it is found elevated in most tumors investigated and rapidly proliferating tissues. With the elucidation of the structure of the catalytic subunit, it was possible to explain why the enzyme is constitutively active [1] and why it can bind GTP [2]. Considerable information on the potential roles of CK2 in various disease processes including cancer has been gained in recent years, and the present review may help to further elucidate its aberrant role in many disease states. Its peculiar structural features [3-9] may be advantageous in designing tailor-made compounds with the possibility to specifically target this protein kinase [10]. Since not all the aspects of what has been published on CK2 can be covered in this review, we would like to recommend the following reviews; (i) for general information on CK2 [11-18] and (ii) with a focus on aberrant CK2 [19-22].

Topics: Casein Kinase II; Humans; Neoplasms; Nervous System Diseases; Protein Subunits; Signal Transduction

Neurofibrillary tangles (NFT) are pathological cytoskeletal structures composed of paired helical filaments (PHF), and are found in neurons of patients afflicted with many neurodegenerative disorders, including Alzheimer's disease (AD). We previously found that an antiserum against casein kinase II (CK-II) stained NFT intensely in the brain tissue of AD patients. In the current study, we found that the anti-CK-II antiserum stains NFT and neuronal inclusions in many other neurodegenerative diseases as well, including Guam-Parkinson dementia complex, chromosome 18 deletion syndrome, progressive supranuclear palsy, Kufs' disease, and Pick's disease. This antiserum reacted, in crude brain homogenates, with both a doublet of Mr 43,000 and a Mr 27,000 Da protein which could correspond to the alpha, alpha', and beta chains of CK-II. The staining of these bands was adsorbed by preincubating anti-CK-II antiserum with purified CK-II. Preincubation of brain sections with purified CK-II strongly intensified the immunostaining of NFT with anti-CK-II, suggesting that NFT may bind CK-II. In the AD brain homogenates, the particulate CK-II levels are increased whereas the cytosolic levels are decreased without a change in total CK-II levels, consistent with the idea that CK-II binds to the particulate PHF, a major constituent of NFT. In accord with these findings, purified PHF bound CK-II, but purified PHF did not contain CK-II as its component. These results suggest that CK-II might be an extraneously deposited component of NFT. Thus, the altered CK-II compartmentalization might have significant consequences in the pathogenesis of AD.

Topics: Brain; Casein Kinase II; Cytoplasm; Humans; Immunoblotting; Immunohistochemistry; Intermediate Filaments; Nerve Degeneration; Nervous System Diseases; Neurofibrillary Tangles; Protein Serine-Threonine Kinases