Department of Anesthesiology

You are here

Characterization in mammalian brain of a DARPP-32 serine kinase identical to casein kinase II.

TitleCharacterization in mammalian brain of a DARPP-32 serine kinase identical to casein kinase II.
Publication TypeJournal Article
Year of Publication1990
AuthorsGirault JA, Hemmings HC, Zorn SH, Gustafson EL, Greengard P
JournalJ Neurochem
Volume55
Issue5
Pagination1772-83
Date Published1990 Nov
ISSN0022-3042
KeywordsAnimals, Animals, Newborn, Brain, Casein Kinases, Caudate Nucleus, Dopamine and cAMP-Regulated Phosphoprotein 32, Immunohistochemistry, Male, Nerve Tissue Proteins, Phosphoproteins, Protein Kinases, Protein-Serine-Threonine Kinases, Putamen, Rats, Rats, Inbred Strains, Subcellular Fractions, Tissue Distribution
Abstract

DARPP-32, a dopamine- and cyclic AMP-regulated phosphoprotein of Mr 32,000, is phosphorylated in vitro by casein kinase II at a site which is also phosphorylated in intact cells. In the present study, we show that a protein kinase activity, present in caudate-putamen cytosol, phosphorylates DARPP-32 on a seryl residue located on the same thermolytic peptide that is phosphorylated by purified casein kinase II. This DARPP-32 serine kinase was indistinguishable from casein kinase II on the basis of a number of biochemical criteria. Excitotoxic lesions of the caudate-putamen and immunocytochemistry revealed the presence of casein kinase II in the medium-sized striatonigral neurons which are known to contain DARPP-32. Casein kinase II activity was high in all rat brain regions studied, and casein kinase II-like immunoreactivity was detected in most brain neurons, although some neuronal populations (e.g., cortical pyramidal cells and large striatal neurons) were stained more intensely than others. In rat caudate-putamen, 45% of the total casein kinase II activity was in the cytosol and 20% in the synaptosomal fraction. In mouse cerebral cortex and caudate-putamen, casein kinase II activity was high at embryonic day 16, and remained elevated during development. In addition to DARPP-32, several major substrates for casein kinase II were observed specifically in brain, but not in liver extracts. The high activity of casein kinase II in brain from the embryonic period to adult age and the existence of a number of specific substrates suggest that this enzyme may play an important role in both developing and mature brain, possibly in modulating the responsiveness of target proteins to various extracellular signals.

Alternate JournalJ. Neurochem.
PubMed ID2145398
Grant ListMH-40899 / MH / NIMH NIH HHS / United States