Disease relevance of GNA11

• Electrophoretic analysis of the proteins bound to poly(3-hydroxybutyric acid), PHB-, granules in Methylobacterium extorquens, M. rhodesianum as well as the PHB-leaky mutants Mu 1 and Mu 11, which were isolated from the latter, resulted in two dominant low-molecular weight proteins, which were referred to as GA11 and GA20 [1].

High impact information on GNA11

• However, reconstitution was not observed with cells that overexpressed G alpha q or G alpha 11 [2].
• Here, we report TCR.CD3-mediated guanine nucleotide exchange among the 42-kDa G protein alpha subunits of the G alpha q/11 family, their physical association with CD3 epsilon, and the G alpha 11-dependent activation of phospholipase C beta [3].
• Quite interesting is the observation that cells transfected with a function-deficient mutant of G alpha 11 display diminished tyrosine phosphorylation of TCR.CD3 zeta and epsilon chains, as well as ZAP-70, upon anti-CD3 antibody triggering [3].
• However, cells cotransfected with the cDNA encoding G alpha q, G alpha 11, or G alpha 14 instead of G alpha 16 gave no ligand-dependent activation of phospholipase C (PLC) [4].
• High efficiency transient transfection of Cos-7 cells was previously used to establish the functional coupling between G alpha q/G alpha 11 and phospholipase C beta 1 (Wu, D., Lee, C-H., Rhee, S. G., and Simon, M. I. (1992) J. Biol. Chem. 267, 1811-1817) [5].

Biological context of GNA11

• GNA11 is involved in signalling of gonadotropin-releasing hormone receptor, which negatively regulates cell growth [6].
• Methylation of a CpG island (CGI) in the 5' region of GNA11 or that of intron 1 did not show a clear correlation with its decreased expression [6].
• Therefore G alpha 11 gene expression in haematopoietic cells is linked with cellular differentiation [7].
• To define their roles in platelet activation we studied G alpha q and G alpha 11 gene expression by immunotransfer blotting and by reverse transcription of mRNA followed by PCR (RT-PCR) and direct sequencing [7].
• Membranes derived from G alpha q and G alpha 11, but not G alpha OA transfected cells, showed guanosine 5-O-thiotriphosphate (GTP gamma S)-stimulated PIP2 hydrolysis [8].

Anatomical context of GNA11

• Specificity of G alpha q and G alpha 11 gene expression in platelets and erythrocytes. Expressions of cellular differentiation and species differences [7].
• The activity seen in the system reconstituted with membranes derived from G alpha 11-transfected cells was blocked by preincubation with specific G alpha 11 antipeptide antibodies [8].
• The cotransfection of Cos-7 cells with cDNAs encoding three different alpha 1-adrenergic receptors and G alpha q or G alpha 11 leads to an increase in norepinephrine-dependent inositol phosphate release [5].
• We report that human myometrium contains G alpha i1, G alpha i3, and G alpha q, and G alpha 11, which are expressed at similar levels in tissues from pregnant and nonpregnant women [9].
• These findings suggest that G proteins, and the signals they regulate, such as ion channels and/or adenylate cyclase (G alpha s/i) and phospholipase C (G beta gamma and G alpha 11/16) are differentially regulated in lymphoid cells in a maturation-and lineage-dependent manner [10].

Associations of GNA11 with chemical compounds

• RT-PCR performed with gene-specific primers demonstrated G alpha q mRNA, but not G alpha 11 mRNA, in normal human and mouse platelets and in thromboxane-sensitive and thromboxane-insensitive dog platelets [7].
• Cells that were prelabeled with the [3H]inositol and transfected with G alpha q and G alpha 11 cDNA showed marked increases in formation of [3H]inositol phosphates after stimulation with aluminum fluoride [8].
• All of these results are consistent with the conclusion that G alpha q and G alpha 11 cDNA encode proteins that in the presence of GTP gamma S specifically activate PI-PLC [8].
• Moreover, the catalytic activities of the recombinant enzyme were indistinguishable from those of native turkey erythrocyte PLC-beta in assays carried out in the presence of cholate and Ca2+, or in assays of activity after reconstitution with G alpha 11 or G-protein beta gamma-subunits [11].

Regulatory relationships of GNA11

• Molecular cloning, expression and regulatory activity of G alpha 11- and beta gamma-subunit-stimulated phospholipase C-beta from avian erythrocytes [11].
• In contrast, G alpha 11 promoted only a small elevation in the catalytic rate of recombinant PLC-beta 2, which was also typical of the native isoenzyme [12].

Other interactions of GNA11

• Reduced expression of GNA11 and silencing of MCT1 in human breast cancers [6].
• Immunoreactive GTP-binding proteins, G alpha q and G alpha 11, and phospholipase-C beta 3 isoforms were present in myometrial membranes [13].
• Screening of candidate oncogenes in human thyrotroph tumors: absence of activating mutations of the G alpha q, G alpha 11, G alpha s, or thyrotropin-releasing hormone receptor genes [14].
• Concentration of enzyme-dependent activation of PLC-beta 1 and PLC-beta 2 by G alpha 11 and beta gamma-subunits [12].

References