THE DISTRIBUTION AND BIOCHEMICAL-PROPERTIES OF A CDC2-RELATED KINASE,KKIALRE, IN NORMAL AND ALZHEIMER BRAINS

The biochemical properties and distribution of a Cdc2-related kinase, KKIALRE, were studied in brain tissues and cultured cells with antibod ies to a subregion of KKIALRE protein deduced from cDNA. In adult huma n brain, the KKIALRE-immunoreactive protein consisted of four or five isoforms having a molecular size of 40-52 kDa, whereas in fetal brain, there was one protein of similar to 48 kDa. Cultured astrocytes, neur oblastoma cells, and mouse brains contained the fetal form of KKIALRE protein. KKIALRE-immunoreactive proteins were capable of phosphorylati ng histone and synthetic peptides with the X-Ser-Pro-X motif, indicati ng that these proteins belong to the proline-directed Ser/Thr protein kinase family. The KKIALRE immunoreactivity was detected primarily in fibrous astrocytes in white matter and perivascular and subpial spaces , as well as in Bergmann glia in the cerebellum. In fetal brains radia l glia were weakly immunoreactive. Reactive astrocytes were more inten sely labeled than other glia. Neurons in normal brains and brains with Alzheimer's disease (AD) displayed no KKIALRE immunoreactivity. KKIAL RE immunoreactivity was similar in neurons with and without neurofibri llary tangles. The results indicate that in CNS, the KKIALRE protein i s mainly a glial protein that is up-regulated in gliosis and that it p robably plays no role in the hyperphosphorylation of tau in AD brains.