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Phosphorylation of the GABAA receptor by cAMP-dependent protein kinase and by protein kinase C: Analysis of the substrate domain

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Abstract

Previous work has shown that the GABAA-receptor (GABAA-R) could be phosphorylated by cAMP-dependent protein kinase (PKA), protein kinase C (PKC), and a receptor associated kinase. However, no clear picture has yet emerged concerning the particular subunit subtypes of the GABAA-R that were phosphorylated by PKA and PKC. In the present report we show that an antibody raised against a 23 amino acid polypeptide corresponding to a sequence in the putative intracellular loop of the β1 subunit of the receptor blocks the in vitro phosphorylation of the purified receptor by PKA and PKC. Moreover, N-terminal sequence analysis of the principal phosphopeptide fragment obtained after proteolysis of the receptor yielded a sequence that corresponds to the β3 subunit of the receptor. Such data provide additional support for our hypothesis (Browning et al., 1990, Proc. Natl. Acad. Sci. USA 87:1315–1317) that both PKA and PKC phosphorylate the β-subunit of the GABAA-R.

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Authors and Affiliations

  1. Department of Pharmacology, University of Colorado Health Sciences Center, 4200 East 9th Street, 80222, Denver, CO

    Michael D. Browning & Ellen M. Dudek

  2. Department of Pharmacology, University of California at Los Angeles, 90024, Los Angeles, CA

    Shuichi Endo, Geoffrey B. Smith & Richard W. Olsen

Authors
  1. Michael D. Browning
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  2. Shuichi Endo
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  3. Geoffrey B. Smith
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  4. Ellen M. Dudek
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  5. Richard W. Olsen
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Special issue dedicated to Dr. Paul Greengard.

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Browning, M.D., Endo, S., Smith, G.B. et al. Phosphorylation of the GABAA receptor by cAMP-dependent protein kinase and by protein kinase C: Analysis of the substrate domain. Neurochem Res 18, 95–100 (1993). https://doi.org/10.1007/BF00966927

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