title: Myosin light chain phosphorylation facilitates monocyte transendothelial migration by dissociating endothelial adherens junctions.
abstract: OBJECTIVE
  Transendothelial migration (TEM) of monocytes is a crucial step in inflammatory processes such as atherogenesis. Tyrosine phosphorylation of vascular endothelial cadherin (VE-cad) has been implicated in the dissociation of adherens junctions and the increased paracellular permeability of endothelial cells (ECs) that occur during TEM of monocytes. However, the underlying molecular mechanism has not been determined. We tested the hypothesis that the phosphorylation of myosin light chain (MLC) in ECs is crucial for the dissociation of adherens junctions during TEM of monocytes.
  
  
  RESULTS
  Using a combination of biochemical and cellular techniques, we provide evidence for the signal transduction pathways that regulate tyrosine phosphorylation of VE-cad in ECs after the attachment of monocytes. Our findings indicate that after interaction of integrins on THP-1 cells with adhesion molecules on ECs, the induction of the HRas\Raf\MEK\ERK signalling cascade leads to the phosphorylation of MLC. This results in the recruitment of Src to the VE-cad complex and tyrosine phosphorylation of VE-cad, which leads to dissociation of β-catenin from the VE-cad complex, formation of gaps between ECs, and enhancement of THP-1 cell TEM.
  
  
  CONCLUSIONS
  Our studies suggest that monocyte-induced phosphorylation of MLC in ECs enhances TEM of monocytes through dissociation of EC adherens junctions.
authors: Division of Cardiology, Department of Internal Medicine, The University of Texas Health Science Center, 6770 Bertner Ave., C1000, Houston, TX 77030, USA. mehran.haidari@uth.tmc.edu
authors: Mehran
authors: M
authors: Haidari
authors: Wei
authors: W
authors: Zhang
authors: Zhenping
authors: Z
authors: Chen
authors: Leila
authors: L
authors: Ganjehei
authors: Navin
authors: N
authors: Warier
authors: Peter
authors: P
authors: Vanderslice
authors: Richard
authors: R
authors: Dixon
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism*; D015703:Antigens, CD / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002460:Cell Line; D018932:Chemokine CCL2 / Q000378:metabolism; D018920:Coculture Techniques; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D051418:Focal Adhesion Kinase 2 / Q000235:genetics / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism*; D018994:Myosin Light Chains / Q000378:metabolism*; D010766:Phosphorylation; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D013997:Time Factors; D057705:Transendothelial and Transepithelial Migration; D014162:Transfection; D014443:Tyrosine; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D018932:Chemokine CCL2; D048049:Extracellular Signal-Regulated MAP Kinases; D051418:Focal Adhesion Kinase 2; D020930:MAP Kinase Kinase Kinases; D018994:Myosin Light Chains; D016283:Proto-Oncogene Proteins p21(ras); D014443:Tyrosine; D019061:src-Family Kinases; D000099152:Cadherin 5; C111835:CCL2 protein, human; C103547:PTK2B protein, human; C501009:HRAS protein, human