Endothelial Signaling, MARCKS and the Cytoskeleton

Control siRNA



eNOS is targeted to plasmalemmal caveolae, yet the enzyme is also importantly regulated by cytoskeletal proteins, including the Rho family GTPase Rac1.  We have also found that the enigmatic MARCKS protein (myristoylated alanine-rich C-kinase substrate) plays a central role in modulating a broad range of endothelial signaling pathways.


  • Kalwa H, Sartoretto J, Martinelli R, Romero N, Steinhorn B, Tao M, Ozaki K, Carman C, Michel T. A central role for hydrogen peroxide in P2Y1 ADP receptor-mediated cellular responses in vascular endothelium. Proc Natl Acad Sci USA 2014, Mar 4;111(9):3383-8. doi: 10.1073/pnas.1320854111. PDF
  • Kalwa H, Sartoretto JL, Sartoretto S, and Michel T. Angiotensin-II and MARCKS: a hydrogen peroxide-  and Rac1-dependent signaling pathway in vascular endothelium.  J Biol Chem 2012, 287: 29147-29158. PDF
  • Jin B, Lin AJ, Golan DE and Michel T. MARCKS protein mediates hydrogen peroxide regulation of endothelial permeability. Proc Natl Acad Sci USA 2012, 109 (37) 1486414869. PDF
  • Kalwa H and Michel T. The MARCKS protein plays a critical role in phosphatidylinositol 4,5-bisphosphate metabolism and directed cell movement in vascular endothelial cells. J Biol Chem 2011, 286: 2320-2333. PDF
  • Chen H, Levine YC, Golan D, Michel T, Lin A. ANP-initiated cGMP pathways regulate VASP phosphorylation and angiogenesis in vascular endothelium. J Biol Chem. 2007; PDF
  • Levine YC, Li GK, Michel T. Agonist-modulated regulation of AMP-activated protein kinase in endothelial cells: Evidence for an AMPK RAC1 AKT eNOS pathway. J Biol Chem. 2007; 282:20351-20364. PDF
  • Gonzalez E, Kou R, Michel T. Rac1 and modulation of P13-kinase pathways in vascular endothelial cells. J Biol Chem. 2006;281:3210-6. PDF
  • Kou R and Michel T. Epinephrine regulation of eNOS: roles of Rac1 and β3-adrenergic receptors in endothelial NO signaling.  J Biol Chem 2007 282: 13719-29. PDF
  • Chen HJ, Michel T. Insulin signaling in vascular endothelial cells: a key role for heterotrimeric G proteins revealed by siRNA-mediated G beta-1 knockdown. Biochemistry. 2006;45:8023-33. PDF
  • Gonzalez E, Nagiel A, Lin A, Golan DE, Michel T. siRNA-mediated downregulation of caveolin-1 differentially modulates signaling pathways in endothelial cells. J Biol Chem. 2004;279:20659-69. PDF
  •  Kou R, Sartoretto J and Michel T.  Regulation of Rac1 by simvistatin in endothelial cells: differential roles of AMP-activated protein kinase and calmodulin-dependent kinase kinase-β.   J Biol Chem 2009, 2004: 14734-43. PDF