Enhanced cell-substratum adhesion of E-cadherin-expressing cells is mediated by activation of the small GTPase protein, Rac1.
L cell transfectants stably expressing E-cadherin demonstrate a remarkable increase in adherence to extracellular matrix proteins, such as type IV collagen and fibronectin. This enhanced adhesion is mediated by integrin-type cell surface receptors, as assessed by inhibition with anti-receptor antibodies. Both the rate and efficiency of adhesion were enhanced 4- to 5-fold. In contrast, non-specific adhesion processes, such as cell attachment to polylysine-coated substrata, are unaffected by E-cadherin expression. Thus, integrin-mediated but not non-specific adhesion is modulated by E-cadherin expression. L cells expressing mutant E-cadherin molecules either lacking the cytoplasmic domain or bearing an amino acid substitution in the Ca2+-binding motif did not exhibit enhanced adhesion. The amount of collagen receptor, the alpha1 and beta1 integrin, did not change following expression of E-cadherin. Pull-down assays with the Cdc42/Rac interactive binding (CRIB) domain of the Rac effector, p21-activated kinase, revealed increased Rac-GTP levels in cells expressing wild-type E-cadherin. These results suggest that the activation of Rac is involved in the enhancement of integrin-mediated adhesion induced by E-cadherin expression.
Wang
Yuqing
Y
Department of Biochemistry, Internal Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan.
Ohkubo
Tadashi
T
Tsubouchi
Hirohito
H
Ozawa
Masayuki
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001665:Binding Sites / Q000235:genetics; D015820:Cadherins / Q000235:genetics / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D024141:Collagen Type IV / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression; D015151:Immunoblotting; D019012:Integrin beta1 / Q000276:immunology / Q000378:metabolism; D007700:Kinetics; D007739:L Cells; D051379:Mice; D009154:Mutation; D011107:Polylysine / Q000378:metabolism / Q000494:pharmacology; D014162:Transfection; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D015820:Cadherins; D024141:Collagen Type IV; D019012:Integrin beta1; D011107:Polylysine; D020830:rac1 GTP-Binding Protein