title: Phosphorylation of the gap junction protein Connexin43 in CIN III lesions and cervical carcinomas.
abstract: Connexins are proteins that form the connexons, gap junction structures, which allow cells to communicate. Phosphorylation of connexins has been found to impair this communication. Using an antibody specifically recognizing the S279/S282-phosphorylated form of connexin43 (Cx43) for immunohistochemistry, we have analysed Cx43 phosphorylation in normal epithelium, CIN III lesions, and carcinomas of the cervix. We found that in normal epithelium the basal layer was devoid of staining and most of the protein was localized in stratum spinosum and stratum granulosum. In pre-malignant CIN-III lesions Cx43 was strongly phosphorylated, but the basal layer was still negative. In squamous carcinomas, the cells were intensely stained. In these tumours, sites of strong staining were adjacent to less stained regions, suggesting that the tumours are intrinsically heterogeneous. Immunoblotting of proteins extracted from carcinomas with the specific antibody showed the classical pattern of multiple reacting bands, with the appearance of low migrating forms of the protein. Our results suggest that increased S279/S282 phosphorylation of Cx43 is the result of altered tissue structure rather than of cell malignization.
authors.affiliation: Pathologisches Institut der Fakultät für Klinische Medizin Mannheim, Ruprecht-Karls-Universität Heidelberg, Theodor-Kutzer-Ufer 1-3, D-68135 Mannheim, Germany.
authors.forename: Inga
authors.initials: I
authors.lastname: Steinhoff
authors.forename: Kerstin
authors.initials: K
authors.lastname: Leykauf
authors.forename: Uwe
authors.initials: U
authors.lastname: Bleyl
authors.forename: Matthias
authors.initials: M
authors.lastname: Dürst
authors.forename: Angel
authors.initials: A
authors.lastname: Alonso
mesh_terms: D002450:Cell Communication; D018031:Connexin 43 / Q000378:metabolism*; D005260:Female; D006801:Humans; D010766:Phosphorylation; D012694:Serine / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002578:Uterine Cervical Dysplasia / Q000378:metabolism* / Q000473:pathology*
chemical_list: D018031:Connexin 43; D012694:Serine