title: RP1 is a phosphorylation target of CK2 and is involved in cell adhesion.
abstract: RP1 (synonym: MAPRE2, EB2) is a member of the microtubule binding EB1 protein family, which interacts with APC, a key regulatory molecule in the Wnt signalling pathway. While the other EB1 proteins are well characterized the cellular function and regulation of RP1 remain speculative to date. However, recently RP1 has been implicated in pancreatic cancerogenesis. CK2 is a pleiotropic kinase involved in adhesion, proliferation and anti-apoptosis. Overexpression of protein kinase CK2 is a hallmark of many cancers and supports the malignant phenotype of tumor cells. In this study we investigate the interaction of protein kinase CK2 with RP1 and demonstrate that CK2 phosphorylates RP1 at Ser(236) in vitro. Stable RP1 expression in cell lines leads to a significant cleavage and down-regulation of N-cadherin and impaired adhesion. Cells expressing a Phospho-mimicking point mutant RP1-ASP(236) show a marked decrease of adhesion to endothelial cells under shear stress. Inversely, we found that the cells under shear stress downregulate endogenous RP1, most likely to improve cellular adhesion. Accordingly, when RP1 expression is suppressed by shRNA, cells lacking RP1 display significantly increased cell adherence to surfaces. In summary, RP1 phosphorylation at Ser(236) by CK2 seems to play a significant role in cell adhesion and might initiate new insights in the CK2 and EB1 family protein association.
authors.affiliation: Division of Oncology, University Hospital Zurich, Zurich, Switzerland. stennerf@uhbs.ch
authors.forename: Frank
authors.initials: F
authors.lastname: Stenner
authors.forename: Heike
authors.initials: H
authors.lastname: Liewen
authors.forename: Stephan
authors.initials: S
authors.lastname: Göttig
authors.forename: Reinhard
authors.initials: R
authors.lastname: Henschler
authors.forename: Norbert
authors.initials: N
authors.lastname: Markuly
authors.forename: Sascha
authors.initials: S
authors.lastname: Kleber
authors.forename: Michael
authors.initials: M
authors.lastname: Faust
authors.forename: Axel
authors.initials: A
authors.lastname: Mischo
authors.forename: Stefan
authors.initials: S
authors.lastname: Bauer
authors.forename: Martin
authors.initials: M
authors.lastname: Zweifel
authors.forename: Alexander
authors.initials: A
authors.lastname: Knuth
authors.forename: Christoph
authors.initials: C
authors.lastname: Renner
authors.forename: Andreas
authors.initials: A
authors.lastname: Wadle
mesh_terms: D000199:Actins; D000595:Amino Acid Sequence; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D047390:Casein Kinase II / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000235:genetics; D002460:Cell Line; D005136:Eye Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D008869:Microtubule-Associated Proteins; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D011485:Protein Binding; D033081:Shear Strength
chemical_list: D000199:Actins; D015820:Cadherins; D005136:Eye Proteins; D008869:Microtubule-Associated Proteins; C120042:RP1 protein, human; D047390:Casein Kinase II