Relative Functions of Gas and its Extra-large Variant XLαs in the Endocrine System

G alpha s is a ubiquitous signaling protein necessary for the actions of many neurotransmitters, hormones, and autocrine/paracrine factors. Loss-of-function mutations within the gene encoding G alpha s, GNAS, are responsible for multiple human diseases, including Albright's Hereditary Osteodystrophy, progressive osseous heteroplasia, and pseudohypoparathyroidism. Gain-of-function mutations in the same gene are found in various endocrine and nonendocrine tumors and in patients with McCune-Albright Syndrome and fibrous dysplasia of bone. In addition to G alpha s, GNAS gives rise to multiple additional coding and noncoding transcripts. Among those, XL alpha s is a paternally expressed product that is partially identical to G alpha s. This article reviews the cellular actions of G alpha s and XL alpha s, focusing on the significance of XL alpha s relative to G alpha s in mammalian physiology and human disease.