G protein-coupled receptors (GPCRs) are involved in numerous cell signaling pathways including cell proliferation and angiogenesis. Regulator of G protein signaling (RGS) proteins negatively regulate GPCR-induced cellular signals by accelerating the GTPase activity of the G alpha subunits. Several RGS proteins exhibit their function independent to their RGS domain, RGS19 is one of them. RGS19, which belongs to the same family of RGS20, has been reported as a tumor suppressor through inhibition of ERK phosphorylation and deregulated cell cycle. However, previous reports have shown that RGS20 expression does not alter cell proliferation rate or impair serum-dependent ERK phosphorylation. Apart from the primary GTPase accelerating function on Gα_z subunit, the function of RGS20 is u...[ Read more ]

G protein-coupled receptors (GPCRs) are involved in numerous cell signaling pathways including cell proliferation and angiogenesis. Regulator of G protein signaling (RGS) proteins negatively regulate GPCR-induced cellular signals by accelerating the GTPase activity of the G alpha subunits. Several RGS proteins exhibit their function independent to their RGS domain, RGS19 is one of them. RGS19, which belongs to the same family of RGS20, has been reported as a tumor suppressor through inhibition of ERK phosphorylation and deregulated cell cycle. However, previous reports have shown that RGS20 expression does not alter cell proliferation rate or impair serum-dependent ERK phosphorylation. Apart from the primary GTPase accelerating function on Gα_z subunit, the function of RGS20 is unclear. RGS20 was found to be significantly up-regulated in primary human squamous cell carcinoma and metastatic melanoma, indicating possible participation of RGS20 in cancer development. Nevertheless, RGS20 may influence blood vessel formation as it is one of the important events in tumor formation. In order to understand the function of RGS20 in tumorigenesis, we have established RGS20 stable cell lines with HEK293, HeLa and NIH3T3. The full-length RGS20 (FL-RGS20) has shown a differential inhibition effect of melatonin receptor 1 (MT₁R)-induced ERK phosphorylation with that of shortened RGS20 (S-RGS). RGS20 expression, unlike RGS19, does not influence the cell cycle progress or induce autophagy. mRNA level of six angiogenesis related genes were found significantly down-regulated with RGS20 expression using qPCR array. Furthermore, soluble angiogenic factors were not detected in RGS20 expressing cells with aortic ring assay. The serum-induce ERK phosphorylation and co-immunoprecipitation with TPR1 and KSR1 revealed that RGS20 does not influence the Ras signaling cascade.