The long (Gs(alpha)-L) and short (Gs(alpha)-S) variants of the stimulatory guanine nucleotide-binding protein. Do they behave in an identical way?

Abstract

The relative proportions and tissue distribution of the long (G s -L ) and short (G s -S ) variants of the subunit of the stimulatory G-protein (G s ) change under a wide range of metabolic conditions, such as cellular differentiation, ontogenetic development, ageing and various adaptive processes. Although the two variants of G s are generally regarded to be functionally identical, this review summarizes recent experimental support for the non-identical behaviour of these proteins. Similarly, there is no consistent evidence for the functional meaning of these changes as far as regulation of adenylate cyclase activity is concerned. Since it is hard to believe that the complicated scheme of alternative splicing and the energy-consuming synthesis of proteins would be performed for no reason, it is suggested that G s variants might be involved in controlling other effector molecules and processes besides adenylate cyclase and cAMP metabolism. Such an idea is indirectly supported by specific alterations in the G s -L /G s -S ratio under various physiological and pathophysiological conditions.

Albuterol-induced downregulation of Gsα accounts for pulmonary β2-adrenoceptor desensitization in vivo

“…Based on electrophoretic mobility on SDS polyacrylamide gels, two of these proteins represent so-called "long" and "short" Gsα variants that arise through alternative mRNA splicing and are ubiquitously expressed (38,39). The other isoform is probably one of several other splice variants that have a more tissue-specific distribution (40). Significantly, the expression of Gsα (assessed by Western blotting and CTX-catalyzed ADP ribosylation) was reduced (∼50%) in the lung of albuterol-treated rats.…”

A Disruptive Mutation in Exon 3 of the GNAS Gene with Albright Hereditary Osteodystrophy, Normocalcemic Pseudohypoparathyroidism, and Selective Long Transcript Variant Gsα-L Deficiency

“…There are controversial discussions in the literature whether the Gs␣ variants may have evolved to perform different regulatory functions or whether they are normal variants interacting exactly in the same way (31). Therefore, from our study we cannot predict the precise mechanism causing the phenotype of AHO and PHP Ia by the mutation affecting only the long transcript variants.…”

“…Another mechanism explaining the phenotype in our patient would be that tissues may express different ratios of Gs␣-L and Gs␣-S and that the phenotypic signs could be caused by a reduction in Gs␣-L in tissues expressing predominantly this isoform. However, little is known about the relative distribution of both variants in humans in AHO-affected tissues (31).…”

Molecular and Clinical Aspects of Pseudohypoparathyroidism

“…The significance of these differences remains unknown, [43][44][45] but these distinctions imply the existence of as yet undefined roles for these G-proteins. 46 Upstream of exon 1 are alternative first exons that each splice onto exons 2-13 to create novel transcripts. Furthest upstream is an alternative promoter that controls expression of transcripts encoding the secretory protein Nesp55, a chromogranin-like protein.…”