G Protein Diversity: a Distinct Class of Alpha Subunits is Present in Vertebrates and Invertebrates
Overview
Authors
Affiliations
Heterotrimeric guanine nucleotide-binding proteins (G proteins) are integral to the signal transduction pathways that mediate the cell's response to many hormones, neuromodulators, and a variety of other ligands. While many signaling processes are guanine nucleotide dependent, the precise coupling between a variety of receptors, G proteins, and effectors remains obscure. We found that the family of genes that encode the alpha subunits of heterotrimeric G proteins is much larger than had previously been supposed. These novel alpha subunits could account for some of the diverse activities attributed to G proteins. We have now obtained cDNA clones encoding two murine alpha subunits, G alpha q and G alpha 11, that are 88% identical. They lack the site that is ordinarily modified by pertussis toxin and their sequences vary from the canonical Gly-Ala-Gly-Glu-Ser (GAGES) amino acid sequence found in most other G protein alpha subunits. Multiple mRNAs as large as 7.5 kilobases hybridize to G alpha q specific probes and are expressed at various levels in many different tissues. G alpha 11 is encoded by a single 4.0-kilobase message which is expressed ubiquitously. Amino acid sequence comparisons suggest that G alpha q and G alpha 11 represent a third class of alpha subunits. A member of this class was found in Drosophila melanogaster. This alpha subunit, DG alpha q, is 76% identical to G alpha q. The presence of the Gq class in both vertebrates and invertebrates points to a role that is central to signal transduction in multicellular organisms. We suggest that these alpha subunits may be involved in pertussis toxin-insensitive pathways coupled to phospholipase C.
Reed E, Sitikov A, Shin K, Hamanaka R, Cetin-Atalay R, Mutlu G Biochem J. 2024; 481(24):1937-1948.
PMID: 39621448 PMC: 11668492. DOI: 10.1042/BCJ20240317.
Pilch J, Mizera J, Tota M, Donizy P Cancers (Basel). 2024; 16(21).
PMID: 39518110 PMC: 11544895. DOI: 10.3390/cancers16213672.
Critical role of Gα12 and Gα13 proteins in TGF-β-induced myofibroblast differentiation.
Reed E, Sitikov A, Hamanaka R, Cetin-Atalay R, Mutlu G, Mongin A bioRxiv. 2024; .
PMID: 38854083 PMC: 11160726. DOI: 10.1101/2024.05.29.596473.
Gomez-Melero S, Garcia-Maceira F, Garcia-Maceira T, Luna-Guerrero V, Montero-Penalvo G, Caballero-Villarraso J Biomedicines. 2022; 10(2).
PMID: 35203631 PMC: 8962412. DOI: 10.3390/biomedicines10020422.
Gα13 Contributes to LPS-Induced Morphological Alterations and Affects Migration of Microglia.
Bettegazzi B, Bellani S, Cattaneo S, Codazzi F, Grohovaz F, Zacchetti D Mol Neurobiol. 2021; 58(12):6397-6414.
PMID: 34529232 DOI: 10.1007/s12035-021-02553-0.