Histamine stimulates phosphorylation of adherens junction proteins and alters their link to vimentin.
Histamine increases microvascular permeability by creating small transitory (100-400 nm) gaps between adjacent endothelial cells at sites of vascular endothelial (VE)-cadherin-based adhesion. We examined the effects of histamine on the proteins within the VE-cadherin-based adherens junction in primary human umbilical vein endothelial cells. VE-cadherin is linked not only by beta- and alpha-catenin to cortical actin but also by gamma-catenin to the intermediate filament vimentin. In mature human umbilical vein cultures, the VE-cadherin immunoprecipitate contained equivalent amounts of alpha- and beta-catenin, 130% as much beta- as gamma-catenin, and 50% as much actin as vimentin. Within 60 s, histamine decreased the fraction of VE-cadherin in the insoluble portion of the cell lysate by 35 +/- 1.5%. At the same time, histamine decreased the amount of vimentin that immunoprecipitated with VE-cadherin by 50 +/- 6%. Histamine did not affect the amount of actin or the amount of alpha-, beta-, or gamma-catenin that immunoprecipitated with VE-cadherin. Within 60 s, histamine simulated a doubling in the phosphorylation of VE-cadherin and beta- and gamma-catenin. The VE-cadherin immunoprecipitate contained kinase activity that phosphorylated VE-cadherin and gamma-catenin in vitro.
Shasby
D Michael
DM
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA. michael.shasby@uiowa.edu
Ries
Dana R
DR
Shasby
Sandra S
SS
Winter
Michael C
MC
D000199:Actins / Q000378:metabolism; D022005:Adherens Junctions / Q000187:drug effects / Q000378:metabolism*; D015703:Antigens, CD; D015820:Cadherins / Q000378:metabolism; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D051180:Desmoplakins; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011233:Precipitin Tests; D015534:Trans-Activators; D014746:Vimentin / Q000378:metabolism*; D051178:alpha Catenin; D051176:beta Catenin; D051185:gamma Catenin; D000099152:Cadherin 5
D000199:Actins; D015703:Antigens, CD; D015820:Cadherins; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; D006632:Histamine; D008565:Membrane Proteins; D015534:Trans-Activators; D014746:Vimentin; D051178:alpha Catenin; D051176:beta Catenin; D051185:gamma Catenin; D000099152:Cadherin 5; C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; C495292:JUP protein, human