title: Identification of novel interaction between annexin A2 and keratin 17: evidence for reciprocal regulation.
abstract: Keratins are cytoplasmic intermediate filament proteins providing crucial structural support in epithelial cells. Keratin expression has diagnostic and even prognostic value in disease settings, and recent studies have uncovered modulatory roles for select keratin proteins in signaling pathways regulating cell growth and cell death. Elevated keratin expression in select cancers is correlated with higher expression of EGF receptor (EGFR), whose overexpression and/or mutation give rise to cancer. To explore the role of keratins in oncogenic signaling pathways, we examined the regulation of epithelial growth-associated keratin 17 (K17) in response to EGFR activation. K17 is specifically up-regulated in detergent-soluble fraction upon EGFR activation, and immunofluorescence analysis revealed alterations in K17-containing filaments. Interestingly, we identified AnxA2 as a novel interacting partner of K17, and this interaction is antagonized by EGFR activation. K17 and AnxA2 proteins show reciprocal regulation. Modulating expression of AnxA2 altered K17 stability, and AnxA2 overexpression delays EGFR-mediated change in K17 detergent solubility. Down-regulation of K17 expression, in turn, results in decreased AnxA2 phosphorylation at Tyr-23. These findings uncover a novel interaction involving K17 and AnxA2 and identify AnxA2 as a potential regulator of keratin filaments.
authors.affiliation: Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA.
authors.forename: Byung-Min
authors.initials: BM
authors.lastname: Chung
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Murray
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Van Eyk
authors.forename: Pierre A
authors.initials: PA
authors.lastname: Coulombe
mesh_terms: D000818:Animals; D017306:Annexin A2 / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D006224:Cricetinae; D004789:Enzyme Activation / Q000502:physiology; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D053537:Keratin-17 / Q000096:biosynthesis* / Q000235:genetics; D055550:Protein Stability
chemical_list: C472822:ANXA2 protein, human; D017306:Annexin A2; D053537:Keratin-17; C512478:EGFR protein, human; D066246:ErbB Receptors