biostudies-literatureUnknown291(23)Kakade PSKeratins 8/18 (K8/18) are phosphoglycoproteins and form the major intermediate filament network of simple epithelia. The three O-GlcNAcylation (Ser(29), Ser(30), and Ser(48)) and two phosphorylation (Ser(33) and Ser(52)) serine sites on K18 are well characterized. Both of these modifications have been reported to increase K18 solubility and regulate its filament organization. In this report, we investigated the site-specific interplay between these two modifications in regulating the functional properties of K18, like solubility, stability, and filament organization. An immortalized hepatocyte cell line (HHL-17) stably expressing site-specific single, double, and triple O-GlcNAc and phosphomutants of K18 were used to identify the site(s) critical for regulating these functions. Keratin 18 The Journal of biological chemistry12003-13https://www.ebi.ac.uk/biostudies/studies/S-EPMC4933253biostudies-literatureFunctional Implications of O-GlcNAcylation-dependent Phosphorylation at a Proximal Site on Keratin 18.PMC4933253Vaidya MMBudnar SKakade PSKalraiya RDfalseFunctional Implications of O-GlcNAcylation-dependent Phosphorylation at a Proximal Site on Keratin 18.Keratins 8/18 (K8/18) are phosphoglycoproteins and form the major intermediate filament network of simple epithelia. The three O-GlcNAcylation (Ser(29), Ser(30), and Ser(48)) and two phosphorylation (Ser(33) and Ser(52)) serine sites on K18 are well characterized. Both of these modifications have been reported to increase K18 solubility and regulate its filament organization. In this report, we investigated the site-specific interplay between these two modifications in regulating the functional properties of K18, like solubility, stability, and filament organization. An immortalized hepatocyte cell line (HHL-17) stably expressing site-specific single, double, and triple O-GlcNAc and phosphomutants of K18 were used to identify the site(s) critical for regulating these functions. Keratin 18 2016-01-01T00:00:00Z2016 Jun2025-04-22T02:15:55.883Z2019-03-27T02:17:36ZS-EPMC49332532705995510.1074/jbc.m116.72871710.1074/jbc.M116.728717