Characterization of Protein Kinase A and Protein Kinase C Phosphorylation of the N-Methyl-D-aspartate Receptor NR1 Subunit Using Phosphorylation Site-specific Antibodies
| Autor: | Kimihiko Kameyama, Michael D. Ehlers, Whittemore G. Tingley, Clark T. Riley, Richard L. Huganir, Carol A. Doherty, Janine Ptak |
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| Rok vydání: | 1997 |
| Předmět: |
inorganic chemicals
Molecular Sequence Data Gi alpha subunit macromolecular substances Biochemistry Antibodies Phosphorylation cascade Receptors Amino Acid Protein phosphorylation Amino Acid Sequence Phosphorylation Protein kinase A Molecular Biology Protein Kinase C Protein kinase C Serine/threonine-specific protein kinase Binding Sites Chemistry musculoskeletal neural and ocular physiology Cell Biology Cyclic AMP-Dependent Protein Kinases nervous system sense organs cGMP-dependent protein kinase |
| Zdroj: | Journal of Biological Chemistry. 272:5157-5166 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.272.8.5157 |
| Popis: | Modulation of N-methyl-D-aspartate receptors in the brain by protein phosphorylation may play a central role in the regulation of synaptic plasticity. To examine the phosphorylation of the NR1 subunit of N-methyl-D-aspartate receptors in situ, we have generated several polyclonal antibodies that recognize the NR1 subunit only when specific serine residues are phosphorylated. Using these antibodies, we demonstrate that protein kinase C (PKC) phosphorylates serine residues 890 and 896 and cAMP-dependent protein kinase (PKA) phosphorylates serine residue 897 of the NR1 subunit. Activation of PKC and PKA together lead to the simultaneous phosphorylation of neighboring serine residues 896 and 897. Phosphorylation of serine 890 by PKC results in the dispersion of surface-associated clusters of the NR1 subunit expressed in fibroblasts, while phosphorylation of serine 896 and 897 has no effect on the subcellular distribution of NR1. The PKC-induced redistribution of the NR1 subunit in cells occurs within minutes of serine 890 phosphorylation and reverses upon dephosphorylation. These results demonstrate that PKA and PKC phosphorylate distinct residues within a small region of the NR1 subunit and differentially affect the subcellular distribution of the NR1 subunit. |
| Databáze: | OpenAIRE |
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