GTPase Activating Specificity of RGS12 and Binding Specificity of an Alternatively Spliced PDZ (PSD-95/Dlg/ZO-1) Domain

摘要: Regulator of G-protein signaling (RGS) proteins increase the intrinsic guanosine triphosphatase (GTPase) activity alpha subunits in vitro, but how specific G-protein-coupled receptor systems are targeted for down-regulation by RGS remains uncharacterized. Here, we describe GTPase specificity RGS12 and identify four alternatively spliced forms human mRNA. Two isoforms 6.3 5.7 kilobases (kb), encoding both an N-terminal PDZ (PSD-95/Dlg/ZO-1) domain domain, expressed most tissues, with highest levels observed testis, ovary, spleen, cerebellum, caudate nucleus. The 5.7-kb isoform has alternative 3' end a putative C-terminal docking site. smaller isoforms, 3.1 3.7 kb, which lack encode without end, respectively, abundantly brain, kidney, thymus, prostate. In vitro biochemical assays indicate that is GTPase-activating protein Gi class subunits. Biochemical interaction trap experiments suggest N terminus acts as classical binding selectively to (A/S)-T-X-(L/V) motifs found within interleukin-8 B (CXCR2) exon form RGS12. presence suggests mechanism may target desensitization.