Phosphorylation of a tyrosine at the N-terminus regulates the surface expression of GIRK5 homomultimers.
The G protein-coupled inwardly rectifying GIRK5 and Delta5GIRK5 splicing variants do not express functional potassium channels. In contrast, Delta25GIRK5 forms functional homomultimers in Xenopus laevis oocytes. A tyrosine is present at the N-term of the non-functional isoforms. We studied the effect of endogenous tyrosine phosphorylation on the GIRK5 surface and functional expression. Unlike wild type channels, GIRK5Y16A and Delta5GIRK5Y16A mutants displayed inwardly rectifying currents and inhibitors of Src tyrosine kinase promoted the traffiking of GIRK5 to the cell surface. This is the first evidence that endogenous phosphorylation of a tyrosine residue in a GIRK channel inhibits its surface expression.
Mora
S Ivonne
SI
Departamento de Fisiologia, Facultad de Medicina, Universidad Nacional Autonoma de Mexico, 04510 Mexico, DF.
Escobar
Laura I
LI
D000595:Amino Acid Sequence; D000818:Animals; D016227:Benzoquinones; D002462:Cell Membrane / Q000378:metabolism*; D004594:Electrophysiology; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D044387:GTP-Binding Protein beta Subunits / Q000378:metabolism; D044388:GTP-Binding Protein gamma Subunits / Q000378:metabolism; D005786:Gene Expression Regulation; D047029:Lactams, Macrocyclic; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000235:genetics / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011809:Quinones / Q000494:pharmacology; D029867:Xenopus Proteins; D014982:Xenopus laevis
D016227:Benzoquinones; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C118981:G-protein Beta gamma; C489498:GIRK5 protein, Xenopus; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D047029:Lactams, Macrocyclic; D024661:Potassium Channels, Inwardly Rectifying; D047428:Protein Kinase Inhibitors; D011809:Quinones; D029867:Xenopus Proteins; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; C001277:geldanamycin