Inhibiting the Recruitment of PLCγ1 to Kaposi's Sarcoma Herpesvirus K15 Protein Reduces the Invasiveness and Angiogenesis of Infected Endothelial Cells.

ABSTRACT: Kaposi's sarcoma (KS), caused by Kaposi's sarcoma herpesvirus (KSHV), is a highly vascularised tumour of endothelial origin. KSHV infected endothelial cells show increased invasiveness and angiogenesis. Here, we report that the KSHV K15 protein, which we showed previously to contribute to KSHV-induced angiogenesis, is also involved in KSHV-mediated invasiveness in a PLCγ1-dependent manner. We identified βPIX, GIT1 and cdc42, downstream effectors of PLCγ1 in cell migration, as K15 interacting partners and as contributors to KSHV-triggered invasiveness. We mapped the interaction between PLCγ1, PLCγ2 and their individual domains with two K15 alleles, P and M. We found that the PLCγ2 cSH2 domain, by binding to K15P, can be used as dominant negative inhibitor of the K15P-PLCγ1 interaction, K15P

SUBMITTER: Gramolelli S 

PROVIDER: S-EPMC4546648 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature