Identification of PA2.26 antigen as a novel cell-surface mucin-type glycoprotein that induces plasma membrane extensions and increased motility in keratinocytes.
PA2.26 antigen was identified as a cell-surface protein induced in epidermal carcinogenesis and skin remodeling processes. PA2.26 is expressed in carcinoma cell lines and cultured fibroblasts but absent in nontumorigenic keratinocytes. In tissues, PA2.26 is present in epithelial cells of the choroid plexus, ependyma, glomerulus and alveolus, in mesothelial cells, and in endothelia of lymphatic vessels. Biochemical characterization of PA2.26 protein and sequence analysis of the isolated cDNA demonstrate that PA2.26 antigen is a mucin-like transmembrane glycoprotein. Confocal and immunoelectron microscopy analysis in cultured cells reveal that PA2. 26 is concentrated in actin-rich microvilli and plasma membrane projections, such as filopodia, lamellipodia and ruffles, where it colocalizes with members of the ERM (ezrin, radixin, moesin) family protein. Ezrin and moesin, but not radixin, can be coimmunoprecipitated together with PA2.26 from cell lysates. Ectopic expression of PA2.26 in immortalized, nontumorigenic, keratinocytes induces an epithelial-fibroblastoid morphological conversion with increased plasma membrane extensions, concomitantly to a major reorganization of the actin cytoskeleton, redistribution of ezrin to cell-surface projections, and enhanced motility. These findings suggest an involvement of PA2.26 in cell migration.
Scholl
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FG
Instituto de Investigaciones Biomédicas Alberto Sols CSIC-UAM, Hospital de la Princesa, Facultad de Medicina UAM, Spain.
Gamallo
C
C
Vilaró
S
S
Quintanilla
M
M
D000199:Actins / Q000648:ultrastructure; D000595:Amino Acid Sequence; D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001483:Base Sequence; D002460:Cell Line; D002462:Cell Membrane / Q000648:ultrastructure; D002465:Cell Movement / Q000276:immunology*; D003001:Cloning, Molecular; D018076:DNA, Complementary; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000166:cytology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D016253:Microscopy, Immunoelectron; D008969:Molecular Sequence Data; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D000098853:Podoplanin
D000199:Actins; D000954:Antigens, Surface; D018076:DNA, Complementary; D008562:Membrane Glycoproteins; C490441:Pdpn protein, mouse; D000098853:Podoplanin