Disease relevance of Gna15

• Polyclonal antisera produced from synthetic peptides that correspond to two regions of G alpha 15 react with a protein of 42 kDa expressed in B-cell membranes and in Escherichia coli transformed with G alpha 15 cDNA [1].
• Inflammatory challenges, including thioglycolate-induced peritonitis and infection with Trichinella spiralis, stimulated similar responses in Galpha15(-/-) adults and wild-type siblings [2].
• Ca(2+) signaling was abolished only in mutant cells pretreated with pertussis toxin, suggesting that the C5a receptor couples to both Galpha15 and Galphai in vivo [2].

High impact information on Gna15

• Among hematopoietic cell lines, G alpha 11 mRNA is found in all cell lines tested, G alpha q is expressed widely but is not found in most T-cell lines, G alpha 15 is predominantly expressed in myeloid and B-cell lineages, and G alpha 14 is expressed in bone marrow adherent (stromal) cells, certain early myeloid cells, and progenitor B cells [1].
• Murine G alpha 14 and G alpha 15 cDNAs encode distinct alpha subunits of heterotrimeric guanine nucleotide-binding proteins (G proteins) [1].
• C5a-stimulated phosphoinositide accumulation and Ca(2+) release was significantly reduced in Galpha15(-/-) macrophages [2].
• Agonist-stimulated Ca(2+) release from intracellular stores was assayed to identify signaling defects in primary cultures of thioglycolate-elicited macrophages isolated from Galpha15(-/-) mice [2].
• We disrupted the Galpha15 gene by homologous recombination in embryonic stem cells to identify its biological functions [2].

Biological context of Gna15

• Normal hematopoiesis and inflammatory responses despite discrete signaling defects in Galpha15 knockout mice [2].
• One is a Galphaq in the narrow sense, and the other, termed rat Galpha15, is a rat counterpart of mouse Galpha15, sharing an amino acid sequence similarity of 94% [3].
• A comparison with the mutant Thr370Lys alpha2B AR-Galpha15 fusion protein displayed similar Ca2+ kinetics and a ligand-mediated receptor activation profile characterized by higher potencies and greater maximal Ca2+ responses for the ligands being investigated, including the putative antagonists dexefaroxan and idazoxan [4].

Anatomical context of Gna15

• Identification of two alpha-subunit species of GTP-binding proteins, Galpha15 and Galphaq, expressed in rat taste buds [3].

Associations of Gna15 with chemical compounds

• Activation of the wild-type alpha2B AR-Galpha15 fusion protein in CHO-K1 cells by (-)-adrenaline induced a time- and concentration-dependent (pEC50 = 7.37+/-0.13) increase in the intracellular Ca2+ concentration, which could be antagonized by RX 811059 (pK(B) = 7.55+/-0.15) [4].

Regulatory relationships of Gna15

• Despite discrete signaling defects, compensation by coexpressed Gq and/or Gi class alpha subunits may suppress abnormalities in Galpha15-deficient mice [2].

Other interactions of Gna15

• A recently described large molecular weight G protein, G alpha h (Nakaoka et al., 1994: Science 264:1593-1596), was also present, G alpha 15, G alpha t1, G alpha olf, G alpha oA, G beta 3, G gamma 1, and G gamma 8 mRNA transcripts were not detected using this method [5].

Analytical, diagnostic and therapeutic context of Gna15

• Western blot analysis showed that these cells express three of the four Gq class subunits, Galphaq, Galpha11, and Galpha14 but not Galpha15 [6].
• RT-PCR and Northern blot analysis demonstrated that rat Galpha15 and Galphaq were distinctly expressed in tongue epithelia containing taste buds [3].

References