GNAS
guanine nucleotide binding protein (G protein), alpha stimulating activity polypeptide 1
G protein mediating the actions of many hormones, neurotransmitters, and paracrine/autocrine factors via generation of the second messenger cAMP [Pubmed]
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role in cancer | TSG, oncogene |
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types of alteration in cancer | highly recurrent R201C in pancreatic neoplasia [Pubmed]; highly recurrent R201C in pituitary adenoma [Pubmed] |
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impact of mutation on function | R201C mutation results in the constitutive activation of GNAS and adenylate cyclase and leads to the autonomous synthesis of cyclic adenosine monophosphate (cAMP) [Pubmed] |
proliferative signalling
activation of adenylyl cyclase bypasses the cells' normal requirement for trophic hormone in pituitary adenoma [Pubmed]; GNAS R201C expression was associated with elevated expression of Wnt and extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase (ERK1/2 MAPK) pathway target genes, increased phosphorylation of ERK1/2 MAPK and increased immunostaining for the proliferation marker Ki67 in mouse models [Pubmed]; promotes cell proliferation in RCC [Pubmed]
suppression of growth
suppresses Shh signalling-dependent cell proliferation by regulating both the cAMP-dependent pathway and ciliary trafficking of Hedgehog pathway components in Shh-driven medulloblastoma [Pubmed]