MAP3K8 and glioblastoma: Tpl2 ablation down-regulated PAR1 mediated activation of a variety of proinflammatory and proangiogenic factors including MMPs, VEGF, Cyr61 and SDF1α. In addition to the Tpl2 mediated response, there are reports of thrombin mediated PAR1-G12/13 RhoA activation of phospholipase D (PLD) that, in turn, activated Rap1 in 1321N1 and U373MG glioblastoma cells, which is a well-known Ras-GTPase readily activated in platelets [48].