Disease relevance of GNA15

• The G alpha 16 cDNA encodes a protein with predicted Mr of 43,500, which resembles the G q class of alpha subunits and does not include a pertussis toxin ADP-ribosylation site [1].
• The human Burkitt's lymphoma cell lines Raji, Ramos, BJAB, the lymphoblastoid cell line SKW6.4, and the plasmocytoma cell line U266 were devoid of G alpha 16 [2].
• In this study, we analyzed G alpha 16 expression using a RT-PCR technique by testing elutriated blood cells from normal donors, PBSC from breast cancer patients and bone marrow or peripheral blood cells from acute leukemia patients [3].

High impact information on GNA15

• We suggest that G alpha 16 may act together with free G beta 1 gamma 1 to activate PLC beta 2, while G alpha 16 may form heterotrimeric complexes with G beta 1 gamma 5 and be stabilized in an inactive form [4].
• G alpha 16, a G protein alpha subunit specifically expressed in hematopoietic cells [1].
• The restricted expression of this gene suggests that G alpha 16 regulates cell-type-specific signal-transduction pathways, which are not inhibited by pertussis toxin [1].
• Cell lines of myelomonocytic and T-cell phenotype express the G alpha 16 gene, but no expression is detectable in two B-cell lines or in nonhematopoietic cell lines [1].
• Antisera generated from synthetic peptides that correspond to two regions of G alpha 16 specifically react with a protein of 42- to 43-kDa in bacterial strains that overexpress G alpha 16 and in HL-60 membranes [1].

Biological context of GNA15

• G alpha 16 gene expression is down-regulated in HL-60 cells induced to differentiate to neutrophils with dimethyl sulfoxide [1].
• In comparison with other G protein alpha subunits, the G alpha 16 predicted protein has distinctive amino acid sequences in the amino terminus, the region A guanine nucleotide-binding domain, and in the carboxyl-terminal third of the protein [1].
• Recently G alpha 16, a new guanosine triphosphate (GTP) binding protein alpha subunit has been described to be specifically expressed in human hematopoietic cells [2].
• Chinese hamster ovary cells co-transfected with this cDNA clone and a G-protein alpha subunit (G alpha-16) became functionally responsive to C3a and a C3a analog synthetic peptide, as measured by increased phosphoinositide hydrolysis [5].
• Surprisingly, we found the gene encoding the promiscuously coupling G(alpha15) protein (Gna15) located in tandem just upstream, an arrangement conserved in the human genome (on chromosome 19p13.3) [6].

Anatomical context of GNA15

• COS-7 cells cotransfected with the beta 2-AR cDNA and the G alpha 15 or G alpha 16 cDNA showed marked norepinephrine-induced increases in accumulation of inositol phosphates in a concentration-dependent manner [7].
• In contrast, G alpha 16 was detected in the human progenitor B cell lines Reh and Nalm-6 [2].
• Expression of G alpha 16 was observed in human cell lines of myelomonocytic and T-lymphocytic origin, but not in human B-cell lines Raji and IM9 [2].
• G alpha y was expressed in multiple other cell types and tissues, but G alpha 16 was restricted in expression to keratinocytes and keratinocyte-derived adnexal structures in the skin [8].
• In cells derived from patients, G alpha 16 expression has been detected in progenitor- and pre-B ALL cells and also in peripheral blood stem cells (PBSC) [3].

Associations of GNA15 with chemical compounds

• In addition, stimulation of inositol phosphate formation via receptors naturally coupled to phospholipase C was enhanced by cotransfection of G alpha 15 and G alpha 16 [9].
• Coupling of metabotropic glutamate receptors 2 and 4 to G alpha 15, G alpha 16, and chimeric G alpha q/i proteins: characterization of new antagonists [10].
• HEK-293 cells cotransfected with this clone, and a cDNA encoding G alpha-16 specifically bound (Kd = 1.6+/-0.7 nM) and responded functionally to C3a with an intracellular calcium mobilization (ED50 = 0.18+/-0.02 nM) [11].
• Interestingly, in a mutant with a single exchange of Ser449 to Ala, the signal transduction assessed by a Ca(2+) assay and [(35)S]GTP gamma S-binding on HEK cells transiently co-transfected with G-alpha 16 or G-alpha O, respectively, was severely impaired, indicating that this residue of C3aR is involved in G protein coupling [12].
• In contrast to mastoparan, iC5b67 failed to directly activate G proteins to stimulate inositol phosphate formation in COS cells that had been transfected with G alpha 16 [13].

Physical interactions of GNA15

• G alpha 16 couples chemoattractant receptors to NF-kappa B activation [14].

Regulatory relationships of GNA15

• The synergistic increase in inositol phosphate release in Cos-7 cells after they were cotransfected with cDNAs encoding G alpha subunits and phospholipase C beta 1 indicates that both G alpha 16 and G alpha 14 can activate phospholipase C beta 1 [15].
• Furthermore, we found that coexpression of G alpha 16 and G beta 1 gamma 1 but not G beta 1 gamma 5 in COS-7 cells was able to synergistically activate recombinant PLC beta 2 [4].
• Reconstitution of chemokine-induced activation of PLC indicated coupling of IL-8R alpha and beta to pertussis toxin-insensitive G alpha 16-proteins as well as to pertussis toxin-sensitive G alpha i2- or G alpha i3-proteins [16].

Other interactions of GNA15

• 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) [7].
• The result that the G gamma 3 mutant could not inhibit beta 2-adrenergic receptor-mediated activation of PLC in cells cotransfected with the G alpha 16 cDNA suggests that G beta gamma is unlikely to be a major mediator of beta 2-adrenergic receptor-induced activation of PLC [7].
• Multiple regions of G alpha 16 contribute to the specificity of activation by the C5a receptor [17].
• In contrast, G alpha 16 expression was highest in T cells and pre-B cells and progressively declined with B-cell maturation [18].
• Furthermore, coexpression of G alpha 16 and apoaequorin provides a basis for a generic mammalian cell microplate assay for the assessment of agonist action at virtually any G-protein-coupled receptor, including orphan receptors for which the physiological signal transduction mechanism may be unknown [19].

Analytical, diagnostic and therapeutic context of GNA15

• We studied the expression of G alpha 16 in human B cells corresponding to different stages of B-cell differentiation by means of reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting [2].
• Given that Northern blots demonstrated similar tissue distributions of the mouse s1p(4) and Gna15 transcripts, we propose that transcription of the two genes may be under control of the same enhancer elements and that their protein products may couple in vivo [6].
• G alpha 16 expression was not detected in U-937 cells or in 2A3 cells, either by reverse transcription-polymerase chain reaction or by immunoblotting [20].
• Monitoring of hematopoietic recovery after autologous stem cell transplantation by analysis of G alpha 16 mRNA and CD34 surface glycoprotein [21].

References