Regulation of endothelial cell barrier function by calcium/calmodulin-dependent protein kinase II

Talaibek Borbiev, Alexander Dmitriyevich Verin, Shu Shi, Feng Liu, Joe G N Garcia

Research output: Contribution to journalArticlepeer-review

64 Scopus citations


Thrombin-induced endothelial cell barrier dysfunction is tightly linked to Ca2+-dependent cytoskeletal protein reorganization. In this study, we found that thrombin increased Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) activities in a Ca2+- and time-dependent manner in bovine pulmonary endothelium with maximal activity at 5 min. Pretreatment with KN-93, a specific CaM kinase II inhibitor, attenuated both thrombin-induced increases in monolayer permeability to albumin and decreases in transendothelial electrical resistance (TER). We next explored potential thrombin-induced CaM kinase II cytoskeletal targets and found that thrombin causes translocation and significant phosphorylation of nonmuscle filamin (ABP-280), which was attenuated by KN-93, whereas thrombin-induced myosin light chain phosphorylation was unaffected. Furthermore, a cell-permeable N-myristoylated synthetic filamin peptide (containing the COOH-terminal CaM kinase II phosphorylation site) attenuated both thrombin-induced filamin phosphorylation and decreases in TER. Together, these studies indicate that CaM kinase II activation and filamin phosphorylation may participate in thrombin-induced cytoskeletal reorganization and endothelial barrier dysfunction.

Original languageEnglish (US)
Pages (from-to)L983-L990
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number5 25-5
StatePublished - May 2001
Externally publishedYes


  • Filamin
  • Myosin light chain phosphorylation
  • Thrombin
  • Transendothelial electrical resistance

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology


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