The KSHV G protein-coupled receptor signals via multiple pathways to induce transcription factor activation in primary effusion lymphoma cells

The Gα12/13 Family of Heterotrimeric G Proteins and the Small GTPase RhoA Link the Kaposi Sarcoma-associated Herpes Virus G Protein-coupled Receptor to Heme Oxygenase-1 Expression and Tumorigenesis

“…vGPCR couples functionally to G␣ q , G␣ i , and G␣ 12 families of G␣ proteins and distinctly transduces the signal to several pathways (19,27,44). Here, we show that the induction of HO-1 expression by G␣ 12/13 correlated with the ability of this family of subunits to induce transformation.…”

“…The G␣ 12/13 Family of Heterotrimeric G Proteins Induces Transformation and HO-1 Expression-It has been shown that the ␣ subunits of the G␣ 12/13 , G␣ q/11 , and G␣ i/0 families of heterotrimeric G proteins can transduce signals initiated by vGPCR (27,29,44). Thus, we investigated if any of these subunits per se were capable of inducing transformation when compared with vGPCR in a focus formation assay.…”

“…Instead, it is known that vGPCR activates the small GTPases Rac and Cdc42 and that Rac mediates vGPCR-induced activation of the NFB transcription factor, thus up-regulating the secretion of critical KS cytokines and ultimately paracrine tumorigenesis (28,31). Recent studies indicate a critical role for Rac1 and the phosphatidylinositol 3-kinase/AKT pathways in vGPCR-induced NFB activation (31,66,67) in endothelial cells, but others suggest that in primary effusion lymphoma cells, NFB activation by vGPCR is not substantially mediated by this pathway (27). Instead, a different study shows that vGPCR-induced NFB activation and interleukin-8 secretion are mediated by the RhoA pathway (29).…”

“…New studies show that vGPCR contributes to KS development by switching on a complex network of signaling pathways, including the direct or autocrine/paracrine activation and expression of receptors, cytokines, signaling molecules, and transcription factors (18,26). As other GPCRs, vGPCR activates downstream effectors by coupling to distinct ␣ subunits of heterotrimeric G proteins (27)(28)(29). Among these effectors are the monomeric or small G proteins of the Rho family represented by RhoA, Rac1, and Cdc42 (30).…”

Pathophysiology Defined by Altered Signal Transduction Pathways: The Role of JAK-STAT and PI3K Signaling in Leukemic Large Granular Lymphocytes

“…38 activity in an SFK dependent fashion. [21][22][23] This effect was associated with the ability of virus molecular machinery to inhibit host cell apoptosis. While no definitive viral etiology has been linked with T-LGL, this area is under active investigation.…”