Betacellulin induces angiogenesis through activation of mitogen-activated protein kinase and phosphatidylinositol 3'-kinase in endothelial cell.

SPECIFIC AIMAlthough betacellulin (BTC) is known as a member of the epidermal growth factor (EGF) family, its effect on angiogenesis has not been characterized. We examined the effect of BTC on angiogenic processes and their main intracellular signaling pathways in primary cultured human umbilical vein endothelial cells (HUVECs).PRINCIPAL FINDINGS1. BTC induces ERK1/2 and Akt phosphorylations in HUVECsActivation of MAPK and Akt in endothelial cells plays a crucial role in angiogenesis. We measured the phosphorylation of two MAPKs, ERK1 (p44MAPK) and ERK2 (p42MAPK). BTC (10 ng/mL) increased ERK1/2 phosphorylation as early as 1 min and produced a maximal effect at 5 min (Fig. 1⤻ A). The maximum mean increase in ERK2 phosphorylation was 7.9-fold. BTC (0.3–10 ng/mL) increased ERK1/2 phosphorylation in a dose-dependent manner (Fig. 1B⤻ ). Both BTC (10 ng/mL) and EGF (10 ng/mL) produced a similar level of ERK2 phosphorylation at 5 min (Fig. 1A, B⤻ ). To measure Akt activity, we measured the phosphorylation of A...