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AKTivation of PI3K/AKT/mTOR signaling pathway by KSHV.

Bhatt AP, Damania B - Front Immunol (2013)

Bottom Line: As an obligate intracellular parasite, Kaposi sarcoma-associated herpesvirus (KSHV) relies on the host cell machinery to meet its needs for survival, viral replication, production, and dissemination of progeny virions.KSHV is a gammaherpesvirus that is associated with three different malignancies: Kaposi sarcoma (KS), and two B cell lymphoproliferative disorders, primary effusion lymphoma (PEL) and multicentric Castleman's disease.We review the mechanisms by which KSHV manipulates the PI3K/AKT/mTOR pathway, with a specific focus on B cells.

View Article: PubMed Central - PubMed

Affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill Chapel Hill, NC, USA ; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill Chapel Hill, NC, USA.

ABSTRACT
As an obligate intracellular parasite, Kaposi sarcoma-associated herpesvirus (KSHV) relies on the host cell machinery to meet its needs for survival, viral replication, production, and dissemination of progeny virions. KSHV is a gammaherpesvirus that is associated with three different malignancies: Kaposi sarcoma (KS), and two B cell lymphoproliferative disorders, primary effusion lymphoma (PEL) and multicentric Castleman's disease. KSHV viral proteins modulate the cellular phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway, which is a ubiquitous pathway that also controls B lymphocyte proliferation and development. We review the mechanisms by which KSHV manipulates the PI3K/AKT/mTOR pathway, with a specific focus on B cells.

No MeSH data available.


Related in: MedlinePlus

Viral proteins enhance cell proliferation by autocrine and paracrine mechanisms. Viral and cellular cytokines and growth factors can activate signaling pathways within the cell they are secreted from (autocrine), or on distant cells that may either be uninfected or latently infected with KSHV (paracrine). RTK, receptor tyrosine kinase.
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Figure 3: Viral proteins enhance cell proliferation by autocrine and paracrine mechanisms. Viral and cellular cytokines and growth factors can activate signaling pathways within the cell they are secreted from (autocrine), or on distant cells that may either be uninfected or latently infected with KSHV (paracrine). RTK, receptor tyrosine kinase.

Mentions: KSHV vGPCR activates a plethora of cellular signaling molecules as well as transcription factors, by means of which it promotes transformation in endothelial, epithelial, and fibroblast cells (Figure 2). vGPCR activates pathways such as PLC/PKC, Pyk2/Lyn, ERK, p38, and JNK, downstream of which are transcription factors that control many growth- and angiogenesis-promoting genes. For example, HIF-1α activation resulting from vGPCR-dependent p38 and MAPK signaling activates the VEGF promoter (Sodhi et al., 2000). vGPCR also activates AP-1, NF-AT, and NF-κB transcription factors, which in turn promote expression of a panoply of pro-inflammatory cytokines, growth factors, and adhesion molecules (Couty et al., 2001; Montaner et al., 2001; Schwarz and Murphy, 2001; Pati et al., 2003). The vGPCR-mediated secretion of such a wide array of factors may enhance proliferation and survival in neighboring, uninfected cells in a paracrine manner (Figure 3). Indeed, a recent report demonstrates that cytokines secreted by a small number of vGPCR-positive tumor cells activate signaling pathways in neighboring cells, converging on mTOR-dependent VEGF up-regulation (Jham et al., 2011). Inhibiting paracrine mTOR activity in non-expressing cells abrogated the tumor-promoting activities of vGPCR-expressing cells in vivo. On the other hand, vGPCR expression may directly induce transformation of the cell, due to up-regulated signaling resulting from the same secreted factors. These two methods of transformation may act in concert, rather than in isolation, leading to transformation of both the infected and bystander cells.


AKTivation of PI3K/AKT/mTOR signaling pathway by KSHV.

Bhatt AP, Damania B - Front Immunol (2013)

Viral proteins enhance cell proliferation by autocrine and paracrine mechanisms. Viral and cellular cytokines and growth factors can activate signaling pathways within the cell they are secreted from (autocrine), or on distant cells that may either be uninfected or latently infected with KSHV (paracrine). RTK, receptor tyrosine kinase.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3539662&req=5

Figure 3: Viral proteins enhance cell proliferation by autocrine and paracrine mechanisms. Viral and cellular cytokines and growth factors can activate signaling pathways within the cell they are secreted from (autocrine), or on distant cells that may either be uninfected or latently infected with KSHV (paracrine). RTK, receptor tyrosine kinase.
Mentions: KSHV vGPCR activates a plethora of cellular signaling molecules as well as transcription factors, by means of which it promotes transformation in endothelial, epithelial, and fibroblast cells (Figure 2). vGPCR activates pathways such as PLC/PKC, Pyk2/Lyn, ERK, p38, and JNK, downstream of which are transcription factors that control many growth- and angiogenesis-promoting genes. For example, HIF-1α activation resulting from vGPCR-dependent p38 and MAPK signaling activates the VEGF promoter (Sodhi et al., 2000). vGPCR also activates AP-1, NF-AT, and NF-κB transcription factors, which in turn promote expression of a panoply of pro-inflammatory cytokines, growth factors, and adhesion molecules (Couty et al., 2001; Montaner et al., 2001; Schwarz and Murphy, 2001; Pati et al., 2003). The vGPCR-mediated secretion of such a wide array of factors may enhance proliferation and survival in neighboring, uninfected cells in a paracrine manner (Figure 3). Indeed, a recent report demonstrates that cytokines secreted by a small number of vGPCR-positive tumor cells activate signaling pathways in neighboring cells, converging on mTOR-dependent VEGF up-regulation (Jham et al., 2011). Inhibiting paracrine mTOR activity in non-expressing cells abrogated the tumor-promoting activities of vGPCR-expressing cells in vivo. On the other hand, vGPCR expression may directly induce transformation of the cell, due to up-regulated signaling resulting from the same secreted factors. These two methods of transformation may act in concert, rather than in isolation, leading to transformation of both the infected and bystander cells.

Bottom Line: As an obligate intracellular parasite, Kaposi sarcoma-associated herpesvirus (KSHV) relies on the host cell machinery to meet its needs for survival, viral replication, production, and dissemination of progeny virions.KSHV is a gammaherpesvirus that is associated with three different malignancies: Kaposi sarcoma (KS), and two B cell lymphoproliferative disorders, primary effusion lymphoma (PEL) and multicentric Castleman's disease.We review the mechanisms by which KSHV manipulates the PI3K/AKT/mTOR pathway, with a specific focus on B cells.

View Article: PubMed Central - PubMed

Affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill Chapel Hill, NC, USA ; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill Chapel Hill, NC, USA.

ABSTRACT
As an obligate intracellular parasite, Kaposi sarcoma-associated herpesvirus (KSHV) relies on the host cell machinery to meet its needs for survival, viral replication, production, and dissemination of progeny virions. KSHV is a gammaherpesvirus that is associated with three different malignancies: Kaposi sarcoma (KS), and two B cell lymphoproliferative disorders, primary effusion lymphoma (PEL) and multicentric Castleman's disease. KSHV viral proteins modulate the cellular phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway, which is a ubiquitous pathway that also controls B lymphocyte proliferation and development. We review the mechanisms by which KSHV manipulates the PI3K/AKT/mTOR pathway, with a specific focus on B cells.

No MeSH data available.


Related in: MedlinePlus