Disease relevance of G-salpha60A

• To examine the function of these subunits we have used vaccinia virus vectors to express both proteins in cyc- cells, a murine S49 cell line deficient for Gs alpha activity [1].
• The schistosome clone contains the putative site for ADP-ribosylation by cholera toxin found in Gs alpha but does not contain the ADP-ribosylation site for pertussis toxin present in Gi alpha [2].
• The amounts of G protein integrated into mature virions and of soluble Gs protein secreted into the culture medium were reduced greatly during VSV infection in Drosophila cells [3].

Psychiatry related information on G-salpha60A

• The ability to associate odors with electroshock was abolished when Galphas* was targeted to MB, but not CC, structures, whereas sensorimotor responses to these stimuli remained normal [4].

High impact information on G-salpha60A

• Associative learning disrupted by impaired Gs signaling in Drosophila mushroom bodies [4].
• To integrate these observations, expression of a constitutively activated stimulatory heterotrimeric guanosine triphosphate-binding protein alpha subunit (Galphas*) was targeted to these brain structures [4].
• In this report we demonstrate, by two different methods, that reduction or elimination of protein kinase A activity had no effect on phenotypes generated by activation of Gs alpha pathways in Drosophila wing epithelial cells [5].
• These genetic studies show that the Gs alpha pathway mediates its primary effects by a novel pathway in differentiating, wing epithelial cells [5].
• One of the best-described transmembrane signal transduction mechanisms is based on receptor activation of the alpha subunit of the heterotrimeric G protein Gs, leading to stimulation of adenylyl cyclase and the production of cAMP [5].

Biological context of G-salpha60A

• Seven mutants have been identified that are either complemented by transgenes representing the wild-type dgs gene or contain nucleotide sequence changes resulting in the production of altered Gs(alpha) protein [6].
• Activation of Gs alpha results in the stimulation of adenylate cyclase and an increase in the second messenger cAMP [7].
• Two forms of Drosophila melanogaster Gs alpha are produced by alternate splicing involving an unusual splice site [8].
• Additional Gs alpha transcript heterogeneity reflects the use of multiple polyadenylation sites [8].
• A comparison of the deduced amino acid sequence of SG12 with a variety of different G alpha proteins indicates that all the major structural features characteristic of a Gs alpha protein are present in the S. mansoni gene [2].

Anatomical context of G-salpha60A

• In situ hybridization studies indicate that the Drosophila Gs alpha transcript is localized primarily in the cells of the central nervous system and in the eyes [7].
• In larvae containing a hypomorphic mutation in the dgs gene encoding the Drosophila Gs alpha protein, there is a significant decrease in the number of synaptic boutons and extent of synaptic arborization, as well as defects in the facilitation of synaptic transmission [9].
• In the presynaptic cell, the synaptic vesicle cycle was regulated by Galphas activity; based on FM1-43 dye imaging studies, evoked vesicle fusion rate was increased in both loss and constitutively active Galphas genotypes [10].

Associations of G-salpha60A with chemical compounds

• The interaction between the alpha subunit of G protein Gs (Gsalpha) and the two cytoplasmic domains of adenylyl cyclase (C1 and C2) is a key step in the stimulation of cAMP synthesis by hormones [11].
• By contrast, neither guanine nucleotide-induced activation of adenylyl cyclase nor Gs protein levels were modified [12].

Other interactions of G-salpha60A

• Here, we show that the abundance of DUNC-13 in NMJ synaptic boutons is regulated downstream of GalphaS and Galphaq pathways, which have inhibitory and facilitatory roles, respectively [13].

Analytical, diagnostic and therapeutic context of G-salpha60A

• Manduca tissues also produced putative Gs alpha subunits of 48 and 51 kDa which were coupled to prothoracic gland adenylate cyclase as demonstrated by immunoprecipitation [14].

References