Regulation of urokinase plasminogen activator localization in keratinocytes by calcium ion and E-cadherin.
In keratinocyte culture, the cellular distribution of many adhesion markers and the organization of intercellular junctions are controlled by the calcium ion concentration of the medium. We show in the present study that urokinase plasminogen activator (uPA) localization in the human keratinocyte is similarly dependent upon calcium concentration. At 30 microM calcium, uPA is present throughout the cell, often with a perinuclear concentration. Upon calcium elevation to 1.0 mM, uPA is concentrated along the cell-cell borders, where it colocalizes (at the light microscope level) with E-cadherin. Blocking antibody to E-cadherin delays the calcium-induced redistribution of uPA, in a manner very similar to the previously observed delay in redistribution of several adhesion-related markers, including vinculin, desmoplakin, and beta 1 integrin. These data suggest a link between the redistribution of uPA to the cell-cell borders and the calcium-induced organization of intercellular junctions in the human keratinocyte. The presence of uPA along the intercellular borders suggests that this enzyme may be involved in regulation of epidermal adhesion through proteolysis.
Jensen
P J
PJ
Department of Dermatology, University of Pennsylvania, Philadelphia 19104-6142.
Wheelock
M J
MJ
D000906:Antibodies; D015820:Cadherins / Q000276:immunology / Q000502:physiology*; D002118:Calcium / Q000494:pharmacology*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010727:Phosphoric Diester Hydrolases / Q000494:pharmacology; D012879:Skin Physiological Phenomena; D013347:Subcellular Fractions / Q000201:enzymology; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis / Q000378:metabolism*
D000906:Antibodies; D015820:Cadherins; D010727:Phosphoric Diester Hydrolases; D014568:Urokinase-Type Plasminogen Activator; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D002118:Calcium