Cell-cell adhesion-mediated tyrosine phosphorylation of nectin-2delta, an immunoglobulin-like cell adhesion molecule at adherens junctions.
We have recently found a novel functional unit of cell-cell adhesion at cadherin-based adherens junctions, consisting of at least nectin, an immunoglobulin-like cell adhesion molecule, and afadin, an actin filament-binding protein which connects nectin to the actin cytoskeleton. Among the members of the nectin family, we have found here that nectin-2delta is tyrosine-phosphorylated in response to cell-cell adhesion. Expression of E-cadherin induced tyrosine phosphorylation of nectin-2delta, while disruption of cell-cell adhesion by an anti-E-cadherin antibody reduced the tyrosine phosphorylation of nectin-2delta. An inhibitor specific for Src family kinase or expression of Csk reduced tyrosine phosphorylation of nectin-2delta. In addition, Src kinase tyrosine phosphorylates the recombinant cytoplasmic region of nectin-2delta in vitro. The major tyrosine phosphorylation site of nectin-2delta was Tyr505 in the cytoplasmic region, because the mutant nectin-2delta, of which Tyr505 was replaced by Phe, showed a loss of tyrosine phosphorylation in vivo and in vitro. These results, together with our recent observations, indicate that the cadherin-catenin system and the nectin-afadin system are closely connected to each other. The cadherin-mediated cell-cell adhesion system may link to the activation of a Src family kinase, that is, at least in part, responsible for the tyrosine phosphorylation of the cytoplasmic region of nectin-2delta. Oncogene (2000) 19, 4022 - 4028.
Kikyo
M
M
Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Japan.
Matozaki
T
T
Kodama
A
A
Kawabe
H
H
Nakanishi
H
H
Takai
Y
Y
D000818:Animals; D019556:COS Cells; D015820:Cadherins / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D016895:Culture Media, Serum-Free; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D016547:Kinesins; D008325:Mammary Neoplasms, Experimental / Q000473:pathology; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism; D009218:Myosins; D000075983:Nectins; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000096:biosynthesis; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D019108:Tight Junctions / Q000502:physiology*; D014162:Transfection; D019061:src-Family Kinases / Q000378:metabolism*
C095516:AFDN protein, human; C490657:Afdn protein, mouse; D015820:Cadherins; D015815:Cell Adhesion Molecules; D016895:Culture Media, Serum-Free; D008840:Microfilament Proteins; D000075983:Nectins; D011993:Recombinant Fusion Proteins; C108835:afadin; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; D019061:src-Family Kinases; D009218:Myosins; D016547:Kinesins