Description
MEKK3 is a member of the MEKK family of protein kinases that directly regulate SAPK and ERK pathway but not the p38 pathway. MEKK3 modulates SAPK and ERK activity by activating the upstream targets SEK and MEK1/2, respectively. KSR2 can regulate the activity of MEKK3 and can reduce MEKK3-mediated ERK activation. Knockout of the MEKK3 gene in mice leads to disruption of blood vessel development and the structural integrity of the yolk sac. The blockage of angiogenesis in these mice is not a result of decreased VEGF1 expression but rather due to an intrinsic defect in Mekk3-/-endothelial cells. Thus, MEKK3 is necessary for blood vessel development and may be a possible target for drugs that control angiogenesis