Protein phosphatase 1 is involved in the dissociation of Ca2+/calmodulin‐dependent protein kinase II from postsynaptic densities

Autophosphorylation‐dependent translocation of Ca2+/calmodulin‐dependent protein kinase II (CaM kinase II) to postsynaptic densities (PSDs) from cytosol may be a physiologically important process during synaptic activation. We investigated a protein phosphatase responsible for dephosphorylation of the kinase. CaM kinase II was shown to be targeted to two sites using the gel overlay method in two‐dimensional gel electrophoresis. Protein phosphatase 1 (PP1) was identified to dephosphorylate CaM kinase II from its complex with PSDs using phosphatase inhibitors and activators, and purified phosphatases. The kinase was released from PSDs after its dephosphorylation by PP1.

[1]  P. Siekevitz,et al.  Binding of L‐[3H]Glutamate to Fresh or Frozen Synaptic Membrane and Postsynaptic Density Fractions Isolated from Cerebral Cortex and Cerebellum of Fresh or Frozen Canine Brain , 1986, Journal of neurochemistry.

[2]  M K Bennett,et al.  Biochemical and immunochemical evidence that the "major postsynaptic density protein" is a subunit of a calmodulin-dependent protein kinase. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[3]  H. Schulman,et al.  Neuronal Ca2+/calmodulin-dependent protein kinases. , 1992, Annual review of biochemistry.

[4]  J. Rostas,et al.  Multiple pools and multiple forms of calmodulin-stimulated protein kinase during development: relationship to postsynaptic densities. , 1986, Progress in brain research.

[5]  B. González,et al.  Purification and characterization of a calmodulin-dependent kinase from rat brain cytosol able to phosphorylate tubulin and microtubule-associated proteins. , 1983, The Journal of biological chemistry.

[6]  Alcino J. Silva,et al.  Deficient hippocampal long-term potentiation in alpha-calcium-calmodulin kinase II mutant mice. , 1992, Science.

[7]  R. Colbran,et al.  Interaction of Autophosphorylated Ca2+/Calmodulin-dependent Protein Kinase II with Neuronal Cytoskeletal Proteins , 1995, The Journal of Biological Chemistry.

[8]  T. Yamauchi,et al.  Purification and characterization of active fragment of Ca2+/calmodulin-dependent protein kinase II from the post-synaptic density in the rat forebrain. , 1996, Journal of biochemistry.

[9]  H. Schulman,et al.  The multifunctional calcium/calmodulin-dependent protein kinase: from form to function. , 1995, Annual review of physiology.

[10]  M K Bennett,et al.  Purification and characterization of a calmodulin-dependent protein kinase that is highly concentrated in brain. , 1983, The Journal of biological chemistry.

[11]  R. Nicoll,et al.  An essential role for postsynaptic calmodulin and protein kinase activity in long-term potentiation , 1989, Nature.

[12]  R. Colbran,et al.  Differential Inactivation of Postsynaptic Density‐Associated and Soluble Ca2+/Calmodulin‐Dependent Protein Kinase II by Protein Phosphatases 1 and 2A , 1997, Journal of neurochemistry.

[13]  P. Greengard,et al.  Two calcium/calmodulin-dependent protein kinases, which are highly concentrated in brain, phosphorylate protein I at distinct sites. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[14]  T. Soderling,et al.  Regulatory Properties of Calcium/Calmodulin‐Dependent Protein Kinase II in Rat Brain Postsynaptic Densities , 1989, Journal of neurochemistry.

[15]  Alcino J. Silva,et al.  Autophosphorylation at Thr286 of the alpha calcium-calmodulin kinase II in LTP and learning. , 1998, Science.

[16]  C. MacKintosh,et al.  Inhibitors of protein kinases and phosphatases. , 1994, Trends in biochemical sciences.

[17]  Alcino J. Silva,et al.  Impaired spatial learning in alpha-calcium-calmodulin kinase II mutant mice. , 1992, Science.

[18]  H. Sugiura,et al.  Characterization and autophosphorylation of Ca2+/calmodulin-dependent protein kinase in the postsynaptic density of the rat forebrain , 1993, Brain Research.

[19]  R. Tsien,et al.  Inhibition of postsynaptic PKC or CaMKII blocks induction but not expression of LTP. , 1989, Science.

[20]  T. Fujii,et al.  Independent Protein Kinases Associated with the Rat Cerebral Synaptic Junction: Comparison with Cyclic AMP‐Dependent and Ca2+/Calmodulin‐Dependent Protein Kinases in the Synaptic Junction , 1987, Journal of neurochemistry.

[21]  T Suzuki,et al.  Rapid Translocation of Cytosolic Ca2+/Calmodulin‐Dependent Protein Kinase II into Postsynaptic Density After Decapitation , 1994, Journal of neurochemistry.

[22]  T. Yamauchi,et al.  Purification and Cahracyterization of te Brain Calmodulin-Dependent Protein Kinase (Kinase II), Which Is involved in the Activtion of Tryptophan 5-Monooxygnase , 1983 .

[23]  T. Hirabayashi.  Two-dimensional gel electrophoresis of chicken skeletal muscle proteins with agarose gels in the first dimension. , 1981, Analytical biochemistry.

[24]  T. Yamauchi,et al.  Evidence for three distinct forms of calmodulin‐dependent protein kinases from rat brain , 1980, FEBS letters.

[25]  A Ishida,et al.  A Novel Protein Phosphatase That Dephosphorylates and Regulates Ca2+/Calmodulin-dependent Protein Kinase II* , 1998, The Journal of Biological Chemistry.

[26]  D. Lovinger,et al.  Translocation of Autophosphorylated Calcium/Calmodulin-dependent Protein Kinase II to the Postsynaptic Density* , 1997, The Journal of Biological Chemistry.

[27]  H. Sugiura,et al.  Developmental changes of protein substrates of Ca 2+ / calmodulin-dependent protein kinase II in teh rat forebrain , 1994, Brain Research.

[28]  R. Colbran,et al.  Autophosphorylation-dependent Targeting of Calcium/ Calmodulin-dependent Protein Kinase II by the NR2B Subunit of theN-Methyl- d-aspartate Receptor* , 1998, The Journal of Biological Chemistry.

[29]  J. Goldenring,et al.  Identification of the Major Postsynaptic Density Protein as Homologous with the Major Calmodulin‐Binding Subunit of a Calmodulin‐Dependent Protein Kinase , 1984, Journal of neurochemistry.

[30]  T. Yamauchi,et al.  Phosphorylation-dependent Reversible Association of Ca2+/Calmodulin-dependent Protein Kinase II with the Postsynaptic Densities* , 1997, The Journal of Biological Chemistry.

[31]  P. Greengard,et al.  Evidence that the major postsynaptic density protein is a component of a Ca2+/calmodulin-dependent protein kinase. , 1984, Proceedings of the National Academy of Sciences of the United States of America.