Cloning and characterization of the human gene for the α‐subunit of G_i2, a GTP‐binding signal transduction protein

Abstract

We isolated and characterized human genomic clones encompassing the gene for the a-subunit of Giz, a GTP-binding signal transduction protein abundantly expressed in myeloid cells. The gene is divided into 9 exons and spans 23.5 kb. Exons 2, 6 and 7 encode putative guanine nucleotide-binding domains that are highly conserved among GTP-binding proteins. A polyadenylation signal located within exon 9 predicts an mRNA size (_ 2.3 kb) several hundred bases longer than that of published cDNAs, and consistent with the size seen on RNA blot hybridization. Primer extension and S, nuclease analysis determined a major and several minor transcriptional start sites. The first exon and 5' flanking region are highly G + C rich, contain several GC boxes (SPl transcription factor binding sites), a CAAT box, and lack a TATA box. The presumptive promoter region is thus similar to that of rap and other widely expressed genes.

Reduced beta-adrenergic receptor activation decreases G-protein expression and beta-adrenergic receptor kinase activity in porcine heart.

“…It is noteworthy that the Gia2 gene contains a putative cAMP response element (32). These data, taken together, suggest that Gia2 protein expression may be altered in a manner that reflects adrenergic activation.…”

In vivo stimulation of the beta(2)-adrenergic pathway increases expression of the Gi proteins and the alpha(2)A-adrenergic receptor genes in the pregnant rat myometrium

“…However, up-regulation of G i 2 levels in response to sustained activation of the stimulatory pathway is not a general feature since it has not been observed in NG 108-15 cells exposed to prostaglandin (PG) E 1 or forskolin (McKenzie & Milligan 1990) or in the human neuroblastoma cell line SK-N-MC treated with isoprenaline (Michel et al 1993). Despite these discrepancies, it had been argued that enhanced transcriptional activity of the human G i 2 gene depends on the presence of a cAMP response element like AP2 (Weinstein et al 1988). In addition, in S49 mouse lymphoma cells, Hadcock et al (1990) demonstrated that activation of the stimulatory Figure 2 Time course of changes in G i 2 and G i 3 mRNA values in myometrial membranes of control pregnant rats or following administration of isoproterenol.…”

Desensitization of adenylate cyclase and increase of Gi alpha in cardiac hypertrophy due to acquired hypertension.

“…50 This factor possesses a binding domain in the promotor region of the G^ gene locus. 51 Since an increase of the activity of the sympathetic nervous system has been observed in rats with renal hypertension, 52 it is not unreasonable to hypothesize that the enhanced expression of cardiac Gp roteins in renal hypertensive rats could be initiated by cAMP and AP-2. However, the increase of G^ expression persists to the stage when adenylate cyclase activity is depressed.…”