Gα12 and Gα13: Versatility in Physiology and Pathology

Abstract

G protein-coupled receptors (GPCRs), as the largest family of receptors in the human body, are involved in the pathological mechanisms of many diseases. Heterotrimeric G proteins represent the main molecular switch and receive cell surface signals from activated GPCRs. Growing evidence suggests that Gα12 subfamily (Gα12/13)-mediated signaling plays a crucial role in cellular function and various pathological processes. The current research on the physiological and pathological function of Gα12/13 is constantly expanding, Changes in the expression levels of Gα12/13 have been found in a wide range of human diseases. However, the mechanistic research on Gα12/13 is scattered. This review briefly describes the structural sequences of the Gα12/13 isoforms and introduces the coupling of GPCRs and non-GPCRs to Gα12/13. The effects of Gα12/13 on RhoA and other signaling pathways and their roles in cell proliferation, migration, and immune cell function, are discussed. Finally, we focus on the pathological impacts of Gα12/13 in cancer, inflammation, metabolic diseases, fibrotic diseases, and circulatory disorders are brought to focus.

GPR35 acts a dual role and therapeutic target in inflammation

“…This leads to the activation of a host of downstream transcription factors, notably NF-κB, a major player in the expression of genes encoding inflammatory factors ( 33 ). In the case of Gα12/13, activation leads to Rho-mediated cytoskeleton reorganization, collaborating with Gβγ to regulate immune cell chemotaxis to inflammation sites - these actions primarily result in pro-inflammatory effects ( 34 , 35 ). Gαq coupled with GPR35 directly inhibits the PI3K catalytic subunit and then suppresses Akt activation.…”

The lncRNA TRG-AS1 promotes the growth of colorectal cancer cells through the regulation of P2RY10/GNA13

“…P2RY10 has been demonstrated to activate GNA12/13 signaling, which is crucial for the proliferation of tumor cells [18,17]. To further investigate the downstream pathways of P2RY10, LoVo cells overexpressing GNA13 were generated.…”

“…In addition, high P2RY10 expression can upregulate the expression of GNA12 and GNA13, which are essential for tumor cell proliferation [17]. It has been reported that GNA12/13 activation can accelerate proliferation and tumor formation in small-cell lung carcinoma, ovarian cancer, and hepatocellular carcinoma cells [18]. Therefore, the current study first determined the levels of P2RY10 and lncRNA TRG-AS1 in normal and CRC cell lines, and then explored the functions of TRG-AS1 and P2RY10 in CRC development in vitro and in vivo.…”