Glucosamine Treatment-mediated O-GlcNAc Modification of Paxillin Depends on Adhesion State of Rat Insulinoma INS-1 Cells*

Protein-protein interactions and/or signaling activities at focal adhesions, where integrin-mediated adhesion to extracellular matrix occurs, are critical for the regulation of adhesion-dependent cellular functions. Although the phosphorylation and activities of focal adhesion molecules have been intensively studied, the effects of the O-GlcNAc modification of their Ser/Thr residues on cellular functions have been largely unexplored. We investigated the effects of O-GlcNAc modification on actin reorganization and morphology of rat insulinoma INS-1 cells after glucosamine (GlcN) treatment. We found that paxillin, a key adaptor molecule in focal adhesions, could be modified by O-GlcNAc in INS-1 cells treated with GlcN and in pancreatic islets from mice treated with streptozotocin. Ser-84/85 in human paxillin appeared to be modified by O-GlcNAc, which was inversely correlated to Ser-85 phosphorylation (Ser-83 in rat paxillin). Integrin-mediated adhesion signaling inhibited the GlcN treatment-enhanced O-GlcNAc modification of paxillin. Adherent INS-1 cells treated with GlcN showed restricted protrusions, whereas untreated cells showed active protrusions for multiple-elongated morphologies. Upon GlcN treatment, expression of a triple mutation (S83A/S84A/S85A) resulted in no further restriction of protrusions. Together these observations suggest that murine pancreatic β cells may have restricted actin organization upon GlcN treatment by virtue of the O-GlcNAc modification of paxillin, which can be antagonized by a persistent cell adhesion process.

• Publication year

  2010

• Venue

  Journal of Biological Chemistry

• Publication date

  2010-09-09

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/jbc.M110.129601PMID 20829364PMCID PMC2975224
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Integrin signalling at a glance

  2009cited by this paper
• Integrins in cell migration – the actin connection

  2009cited by this paper
• Cell-matrix adhesion complexes: master control machinery of cell migration.

  2008cited by this paper
• Tetraspanin TM4SF5 mediates loss of contact inhibition through epithelial-mesenchymal transition in human hepatocarcinoma.

  2008cited by this paper
• Microinjection of recombinant O-GlcNAc transferase potentiates Xenopus oocytes M-phase entry.

  2008cited by this paper
• O-GlcNAc modulation at Akt1 Ser473 correlates with apoptosis of murine pancreatic beta cells.

  2008cited by this paper
• A paxillin tyrosine phosphorylation switch regulates the assembly and form of cell-matrix adhesions

  2006cited by this paper
• Modification of p53 with O-linked N-acetylglucosamine regulates p53 activity and stability

  2006cited by this paper
• Glucosamine-induced endoplasmic reticulum dysfunction is associated with accelerated atherosclerosis in a hyperglycemic mouse model.

  2006cited by this paper
• Cell signaling, the essential role of O-GlcNAc!

  2006cited by this paper
• The Hyperglycemia-induced Inflammatory Response in Adipocytes

  2005cited by this paper
• The Hexosamine Signaling Pathway: Deciphering the "O-GlcNAc Code"

  2005cited by this paper
• Methods for the detection of paxillin post-translational modifications and interacting proteins by mass spectrometry.

  2005cited by this paper
• Phosphorylation of paxillin by p38MAPK is involved in the neurite extension of PC-12 cells

  2004cited by this paper
• O-GlcNAc a sensor of cellular state: the role of nucleocytoplasmic glycosylation in modulating cellular function in response to nutrition and stress.

  2004cited by this paper
• Mitogenic signal transduction by integrin- and growth factor receptor-mediated pathways.

  2004cited by this paper
• Paxillin: adapting to change.

  2004cited by this paper
• FAK–Src signalling through paxillin, ERK and MLCK regulates adhesion disassembly

  2004cited by this paper
• Increased O‐glycosylation of insulin signaling proteins results in their impaired activation and enhanced susceptibility to apoptosis in pancreatic β‐cells

  2004cited by this paper
• Paxillin serves as an ERK-regulated scaffold for coordinating FAK and Rac activation in epithelial morphogenesis.

  2004cited by this paper
• Epithelial-mesenchymal transitions in development and pathologies.

  2003cited by this paper
• JNK phosphorylates paxillin and regulates cell migration

  2003cited by this paper
• Apoptosis in the beta cells: cause or consequence of insulin secretion defect in diabetes?

  2002cited by this paper
• Diverse regulation of protein function by O-GlcNAc: a nuclear and cytoplasmic carbohydrate post-translational modification.

  2002cited by this paper
• Nanometer-scale metrology: meeting the nanotechnology measurement challenges

  2002cited by this paper
• Transgenic Mice Overexpressing the Rate‐Limiting Enzyme for Hexosamine Synthesis in Skeletal Muscle or Adipose Tissue Exhibit Total Body Insulin Resistance

  2002cited by this paper
• Glycosylation of Nucleocytoplasmic Proteins: Signal Transduction and O-GlcNAc

  2001cited by this paper
• Hyperglycemia inhibits endothelial nitric oxide synthase activity by posttranslational modification at the Akt site.

  2001cited by this paper
• Paxillin: a focal adhesion-associated adaptor protein

  2001cited by this paper
• Paxillin and focal adhesion signalling

  2000cited by this paper
• Glucose stimulates protein modification by O-linked GlcNAc in pancreatic beta cells: linkage of O-linked GlcNAc to beta cell death.

  2000cited by this paper
• Glucose stimulates protein modification by O-linked GlcNAc in pancreatic β cells: Linkage of O-linked GlcNAc to β cell death

  2000cited by this paper
• Alternative O-glycosylation/O-phosphorylation of the murine estrogen receptor beta.

  2000cited by this paper
• Elevated O-LinkedN-Acetylglucosamine Metabolism in Pancreatic β-Cells

  1999cited by this paper
• Elevated O-linked N-acetylglucosamine metabolism in pancreatic beta-cells.

  1999cited by this paper
• c-Myc Is Glycosylated at Threonine 58, a Known Phosphorylation Site and a Mutational Hot Spot in Lymphomas (*)

  1995cited by this paper
• RNA polymerase II is a glycoprotein. Modification of the COOH-terminal domain by O-GlcNAc.

  1993cited by this paper
• Tyrosine phosphorylation of paxillin and pp125FAK accompanies cell adhesion to extracellular matrix: a role in cytoskeletal assembly

  1992cited by this paper
• Integrins: versatility, modulation, and signaling in cell adhesion.

  1992cited by this paper
• Paxillin: a new vinculin-binding protein present in focal adhesions

  1990cited by this paper
• Multiple low-dose streptozotocin-induced diabetes in the mouse. Evidence for stimulation of a cytotoxic cellular immune response against an insulin-producing beta cell line.

  1984cited by this paper
• Vinculin, an intracellular protein localized at specialized sites where microfilament bundles terminate at cell membranes.

  1980cited by this paper
• Studies on L-glutamine D-fructose 6-phosphate amidotransferase. I. Feedback inhibition by uridine diphosphate-N-acetylglucosamine.

  1967cited by this paper

• O-GlcNAc transferase promotes the nuclear localization of the focal adhesion–associated protein Zyxin to regulate UV-induced cell death

  2022cites this paper
• Overproduction of inter-α-trypsin inhibitor heavy chain 1 after loss of Gα13 in liver exacerbates systemic insulin resistance in mice

  2019cites this paper
• Nuclear stress bodies: Interaction of its components in oncogenic regulation

  2019cites this paper
• O-GlcNAcylation regulates integrin-mediated cell adhesion and migration via formation of focal adhesion complexes

  2018cites this paper
• Glucosamine Downregulates the IL-1β-Induced Expression of Proinflammatory Cytokine Genes in Human Synovial MH7A Cells by O-GlcNAc Modification-Dependent and -Independent Mechanisms

  2016cites this paper
• O-GlcNAcylation, contractile protein modifications and calcium affinity in skeletal muscle

  2014cites this paper
• A correlation between altered O-GlcNAcylation, migration and with changes in E-cadherin levels in ovarian cancer cells.

  2013cites this paper
• Dynamic O-GlcNAcylation and its roles in the cellular stress response and homeostasis

  2013cites this paper
• A Study on the Effect and Mechanism of O-GlcNAc Transferase Mediated O-Glycosylation in Ovarian Cancer Cell Migration

  2013cites this paper
• Short-term glucosamine infusion increases islet blood flow in anesthetized rats

  2013cites this paper
• Mass Spectrometry of Glycoproteins

  2013cites this paper
• Tandem lectin weak affinity chromatography for glycoprotein enrichment.

  2013cites this paper
• Functional regulation of Slug / Snail2 is dependent on GSK‐3β‐mediated phosphorylation

  2012cites this paper
• Cell Adhesion-dependent Serine 85 Phosphorylation of Paxillin Modulates Focal Adhesion Formation and Haptotactic Migration via Association with the C-terminal Tail Domain of Talin*

  2012cites this paper
• The combined effects of menopause and dietary glucosamine on the development of insulin resistance.

  2012cites this paper