Disease relevance of GNA12

• To determine whether the pertussis toxin-insensitive G12 protein is involved in the thrombin-stimulated DNA synthesis, an inhibitory antibody against the C-terminal sequence of G alpha 12 subunit was microinjected into 1321N1 cells [1].

High impact information on GNA12

• NIH 3T3 cells transfected with G alpha 12 cDNA grew in soft agar and were tumorigenic in nude mice [2].
• Expression cDNA cloning of a transforming gene encoding the wild-type G alpha 12 gene product [2].
• There were no apparent mutations in the cloned cDNA in comparison with a G alpha 12 cDNA clone isolated from a normal human epithelial cell library, implying that overexpression alone was sufficient to cause NIH 3T3 cell transformation [2].
• The observed altered growth properties mediated by G alpha 12 showed a certain degree of dependency on serum factors, and its mitogenic potential was also potently inhibited by suramin treatment [2].
• We demonstrate here, using transfection of receptors and G proteins in COS-7 cells, that G alpha 12 selectively couples the thrombin receptor to AP-1-mediated gene expression [3].

Chemical compound and disease context of GNA12

• Pertussis toxin-insensitive G proteins, most likely from G alpha 12 class, cause the activation of several cytoplasmic protein tyrosine kinases [Src, Pyk2 (proline-rich tyrosine kinase 2), and Fak (focal adhesion kinase)] [4].

Biological context of GNA12

• As an addition to genetic information reported earlier, we provide here 20 novel single nucleotide polymorphisms (SNPs) in the region corresponding to a gene encoding alpha subunits of G(12) protein, GNA12, in the Japanese population: 16 in introns, two in the coding region, and two in the 3' flanking region [5].
• Recent analyses have indicated that G alpha 12 and G alpha 13 regulate cytoplasmic as well as nuclear signaling events such as activation of the Jun N-terminal kinase signaling module, Na+/H+ exchangers, focal adhesion assemblies, and transcriptional activation of specific primary response genes [6].
• The data indicate a protective effect of the RMP synchronous administration (by enzyme induction mechanisms) in the preservation of fibrinogen blood levels [7].
• Transfection with antagonist minigenes coding for small peptide antagonists to G alpha 12 and G alpha13 subunits of heterotrimeric G proteins prevented PTH-stimulated activation of PLD, whereas an antagonist minigene to G alphas failed to produce this effect [8].
• In addition to stimulating Gi-Ras-mediated cell proliferation, LPA and S1P induce rapid G alpha 12/13-RhoA-mediated cytoskeletal changes underlying such diverse responses as neurite retraction, cell rounding, and enhanced tumor cell invasiveness [9].

Anatomical context of GNA12

• Here, we describe the isolation of G alpha 12 from rat brain membranes [10].
• Studies with the constitutively activated mutants of G alpha 12 and G alpha 13 have indicated that they stimulate mitogenic signaling pathways leading to the oncogenic transformation of fibroblast cell lines [6].
• In subconfluent monolayers, G alpha 12 and PKC zeta were found at the plasma membrane only along the areas of lateral cell-cell contact [11].
• The present findings indicate that G alpha 12 and PKC zeta may be part of the zonula occludens complex and may locally regulate formation and permeability of tight junctions [11].
• We report that expression of G alpha 12 is selectively decreased in erythrocytes of humans with type 2 diabetes (DM2) and that these erythrocytes fail to release ATP in response to incubation with mastoparan 7 (10 microM), an agent that activates Gi [12].

Associations of GNA12 with chemical compounds

• For isolation of functionally active G alpha 12, it was mandatory to use sucrose monolaurate as a detergent [10].
• Purified G alpha 12 bound guanosine 5'-[gamma-thio]triphosphate slowly and substoichiometrically [10].
• Fatty acid analysis after labeling with [3H]palmitic acid showed that palmitate represents the predominant fatty acid linked to G alpha 12 and G alpha 13 [13].
• Nineteen randomized patients, treated with isoniazid (INH, CAS 54-85-3) for tuberculosis chemoprophylaxis or isoniazid plus rifampicin (RMP, CAS 13292-46-1) combination for tuberculosis therapy, were studied in order to explore the effects of these drugs on fibrinogen and antithrombin III blood levels [7].

Regulatory relationships of GNA12

• G alpha 12 required a higher Mg2+ concentration for AlF4- -induced dissociation from immobilized G beta gamma than did G alpha 13 [10].

Other interactions of GNA12

• This regularly deleted region is bordered by markers GNA12 (3p21.1-p21.3) and VHL (3p25) that were maintained in a fraction of tumors [14].
• Furthermore, the exchange of a few carboxyl-terminal residues of G alpha q by those of G alpha 12 or G alpha o allows the resulting chimeric G alpha subunits (G alpha ql and G alpha qol respectively) to couple Gi-coupled receptors to PLC [15].
• Using specific antisera against subtypes of Gi proteins, we found that ADP stimulated labelling of the G alpha 12 immunoprecipitate, but not of the G alpha 13 precipitate [16].
• Distinct biochemical properties of the native members of the G12 G-protein subfamily. Characterization of G alpha 12 purified from rat brain [10].

References