UM
Constitutive Activation of NF-κB and Secretion of Interleukin-8 Induced by the G Protein-coupled Receptor of Kaposi's Sarcoma-associated Herpesvirus Involve Gα13 and RhoA
Shepard L.W.; Yang M.; Xie P.; Browning D.D.; Voyno-Yasenetskaya T.; Kozasa T.; Ye R.D.
2001-12-07
Source PublicationJournal of Biological Chemistry
ISSN00219258
Volume276Issue:49Pages:45979-45987
AbstractThe Kaposi's sarcoma herpesvirus (KSHV) open reading frame 74 encodes a G protein-coupled receptor (GPCR) for chemokines. Exogenous expression of this constitutively active GPCR leads to cell transformation and vascular overgrowth characteristic of Kaposi's sarcoma. We show here that expression of KSHV-GPCR in transfected cells results in constitutive transactivation of nuclear factor κB (NF-κB) and secretion of interleukin-8, and this response involves activation of Gα and RhoA. The induced expression of a NF-κB luciferase reporter was partially reduced by pertussis toxin and the Gβγ scavenger transducin, and enhanced by co-expression of Gα and to a lesser extent, Gα. These results indicate coupling of KSHV-GPCR to multiple G proteins for NF-κB activation. Expression of KSHV-GPCR led to stress fiber formation in NIH 3T3 cells. To examine the involvement of the Gα-RhoA pathway in KSHV-GPCR-mediated NF-κB activation, HeLa cells were transfected with KSHV-GPCR alone and in combination with the regulator of G protein signaling (RGS) from p115RhoGEF or a dominant negative RhoA(T19N). Both constructs, as well as the C3 exoenzyme from Clostritium botulinum, partially reduced NF-κB activation by KSHV-GPCR, and by a constitutively active Gα(Q226L). KSHV-GPCR-induced NF-κB activation is accompanied by increased secretion of IL-8, a function mimicked by the activated Gα but not by an activated Gα (Q209L). These results suggest coupling of KSHV-GPCR to the Gα-RhoA pathway in addition to other G proteins.
DOI10.1074/jbc.M104783200
URLView the original
Language英語
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Cited Times [WOS]:87   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
AffiliationUniversity of Illinois College of Medicine
Recommended Citation
GB/T 7714
Shepard L.W.,Yang M.,Xie P.,et al. Constitutive Activation of NF-κB and Secretion of Interleukin-8 Induced by the G Protein-coupled Receptor of Kaposi's Sarcoma-associated Herpesvirus Involve Gα13 and RhoA[J]. Journal of Biological Chemistry,2001,276(49):45979-45987.
APA Shepard L.W..,Yang M..,Xie P..,Browning D.D..,Voyno-Yasenetskaya T..,...&Ye R.D..(2001).Constitutive Activation of NF-κB and Secretion of Interleukin-8 Induced by the G Protein-coupled Receptor of Kaposi's Sarcoma-associated Herpesvirus Involve Gα13 and RhoA.Journal of Biological Chemistry,276(49),45979-45987.
MLA Shepard L.W.,et al."Constitutive Activation of NF-κB and Secretion of Interleukin-8 Induced by the G Protein-coupled Receptor of Kaposi's Sarcoma-associated Herpesvirus Involve Gα13 and RhoA".Journal of Biological Chemistry 276.49(2001):45979-45987.
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