Post-translational excision of the carboxyl-terminal segment of CaM kinase phosphatase N and its cytosolic occurrence in the brain.
Ca2+/Calmodulin-dependent protein kinase (CaM kinase) phosphatase, occurring in the cytoplasm of all tissues, dephosphorylates and thereby deactivates multifunctional CaM kinases, such as CaM kinases I, II and IV. In contrast, CaM kinase phosphatase N has been reported to occur almost exclusively in the brain and to be localized in the nucleus in the transfected COS-7 cells, as examined immunocytochemically with antibodies against the carboxyl-terminal segment of the enzyme, indicating its involvement in the deactivation of CaM kinase IV. Here, we show that the majority of the naturally occurring CaM kinase phosphatase N in the brain exists not in the intact form of the enzyme (83.4 kDa) but in a form (61.1 kDa) in which the carboxyl-terminal segment containing nuclear localization signals is deleted, and that it is present mostly in the cytoplasm but a little in the nucleus throughout the central nervous system, although occurring mostly in the nucleus in some large neurons. Strong immunostaining of the enzyme was also observed at postsynaptic density. These findings suggest that CaM kinase phosphatase N is involved in the regulation of not only CaM kinase IV but also CaM kinases II and I.
Kitani
Takako
T
Department of Biochemistry, Asahikawa Medical College, Asahikawa, Japan.
Okuno
Sachiko
S
Nakamura
Yasuhisa
Y
Tokuno
Hironobu
H
Takeuchi
Masayuki
M
Fujisawa
Hitoshi
H
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000201:enzymology*; D019556:COS Cells; D002522:Chlorocebus aethiops; D003600:Cytosol / Q000201:enzymology*; D004260:DNA Repair; D005260:Female; D007150:Immunohistochemistry / Q000379:methods; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010749:Phosphoprotein Phosphatases / Q000235:genetics* / Q000378:metabolism*; D000071636:Protein Phosphatase 2C; D011499:Protein Processing, Post-Translational; D051381:Rats; D017208:Rats, Wistar; D013194:Staining and Labeling; D013347:Subcellular Fractions / Q000201:enzymology; D014018:Tissue Distribution
D010749:Phosphoprotein Phosphatases; C000607482:Ppm1e protein, rat; D000071636:Protein Phosphatase 2C