Vitorino, Philip; Yeung, Stacey; Crow, Ailey; Bakke, Jesse; Smyczek, Tanya; West, Kristina; McNamara, Erin; Eastham-Anderson, Jeffrey; Gould, Stephen; Harris, Seth F.; Ndubaku, Chudi; Ye, Weilan published the artcile< MAP4K4 regulates integrin-FERM binding to control endothelial cell motility>, Safety of 4-(4-Methyl-1-piperazinyl)phenylboronic Acid, the main research area is MAP4K4 moesin talin beta1 integrin vascular endothelial cell migration; angiogenesis inhibitor synthesis MAP4K4 signaling plasma membrane retraction HUVEC.
Cell migration is a stepwise process that coordinates multiple mol. machineries. Using in vitro angiogenesis screens with short interfering RNA and chem. inhibitors, we define here a MAP4K4-moesin-talin-β1-integrin mol. pathway that promotes efficient plasma membrane retraction during endothelial cell migration. Loss of MAP4K4 decreased membrane dynamics, slowed endothelial cell migration, and impaired angiogenesis in vitro and in vivo. In migrating endothelial cells, MAP4K4 phosphorylates moesin in retracting membranes at sites of focal adhesion disassembly. Epistasis analyses indicated that moesin functions downstream of MAP4K4 to inactivate integrin by competing with talin for binding to β1-integrin intracellular domain. Consequently, loss of moesin (encoded by the MSN gene) or MAP4K4 reduced adhesion disassembly rate in endothelial cells. Addnl., α5β1-integrin blockade reversed the membrane retraction defects associated with loss of Map4k4 in vitro and in vivo. Our study uncovers a novel aspect of endothelial cell migration. Finally, loss of MAP4K4 function suppressed pathol. angiogenesis in disease models, identifying MAP4K4 as a potential therapeutic target.
Nature (London, United Kingdom) published new progress about Angiogenesis. 229009-40-9 belongs to class piperazines, and the molecular formula is C11H17BN2O2, Safety of 4-(4-Methyl-1-piperazinyl)phenylboronic Acid.
Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics