Tyrosine kinase phosphorylation of GABA sub(A) receptors

• Published in: Brain research. Molecular brain research. 1995-01, Vol.31 (1-2), p.165-172
• Main Authors: Valenzuela, C F, Machu, T K, McKernan, R M, Whiting, P, VanRenterghem, B B, McManaman, J L, Brozowski, S J, Smith, G B, Olsen, R W, Harris, R A
• Format: Article
• Language: English
• ISSN: 0169-328X

Phosphorylation of purified bovine brain GABA sub(A) receptors by the tyrosine kinase, pp60 super(v-src) was examined. pp60 super(v-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 beta 2 and gamma 2 GABA sub(A) receptor subunits, respectively. Bacterially expressed proteins containing the putative large cytoplasmic loops of the beta 1 and gamma 2L subunits were phosphorylated by pp60 super(v-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 super(36)Cl super(-) uptake in mouse brain membrane vesicles (microsacs). The magnitude of the tyrphostin B-44-induced inhibition of muscimol-stimulated super(36)Cl super(-) uptake was significantly reduced in microsacs that were lysed and resealed under conditions that inhibit phosphorylation. GABA-gated Cl super(-) currents were also inhibited by genistein and tryphostin B-44 in Xenopus oocytes expressing alpha 1 beta 1 and alpha 1 beta 1 gamma 2L subunits. Consequently, protein tyrosine kinase-dependent phosphorylation appears to be another mechanism of regulating the function of GABA sub(A) receptors.