Tyrosine kinase phosphorylation of GABAA receptors

C. Fernando Valenzuela, Tina K. Machu, Ruth M. McKernan, Paul Whiting, Barbara B. VanRenterghem, James L. McManaman, Susan J. Brozowski, Geoffrey B. Smith, Richard W. Olsen, R. Adron Harris

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Phosphorylation of purified bovine brain GABAA receptors by the tyrosine kinase, pp60v-src was examined. pp60v-src phosphorylated two bands of 54-62 kDa and 48-51 kDa that migrated to approximately the same position as bands recognized by antisera against the β2 and γ2 GABAA receptor subunits, respectively. Bacterially expressed proteins containing the putative large cytoplasmic loops of the β1 and γ2L subunits were phosphorylated by pp60v-src, indicating that the phosphorylation sites are located in these subunit domains. The tyrosine kinase inhibitors, genistein and the tyrphostins B-42 and B-44, inhibited muscimol-stimulated 36Cl- uptake in mouse brain membrane vesicles (microsacs). The magnitude of the tyrphostin B-44-induced inhibition of muscimol-stimulated 36Cl- uptake was significantly reduced in microsacs that were lysed and resealed under conditions that inhibit phosphorylation. GABA-gated Cl- currents were also inhibited by genistein and tyrphostin B-44 in Xenopus oocytes expressing α1β1 and α1βγ2L subunits. Consequently, protein tyrosine kinase-dependent phosphorylation appears to be another mechanism of regulating the function of GABAA receptors.

Original languageEnglish
Pages (from-to)165-172
Number of pages8
JournalMolecular Brain Research
Issue number1-2
StatePublished - Jul 1995


  • GABA-A receptor
  • Genistein
  • Phosphorylation
  • Protein tyrosine kinase
  • Src oncogene protein pp60v
  • Tyrosine kinase inhibitor
  • Tyrphostin


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