Role of Tyrosine Phosphorylation in Intermediate Filament Protein Organization♦

A Conserved Rod Domain Phosphotyrosine That Is Targeted by the Phosphatase PTP1B Promotes Keratin 8 Protein Insolubility and Filament Organization
    Open AccessPublished:October 25, 2013DOI:
        ♦ See referenced article, J. Biol. Chem. 2013, 288, 31329–31337
        Intermediate filament (IF) proteins are a class of cytoskeletal proteins. Phosphorylation of IF proteins affects their organization into filaments, as well as their solubility and function. Very little is known about the impact of tyrosine phosphorylation on these proteins. In this Paper of the Week, a team led by M. Bishr Omary and first author Natasha T. Snider at the University of Michigan Medical School in Ann Arbor validated the predicted phosphotyrosine sites on an epithelial IF protein called keratin 8 (K8). Using a number of molecular and pharmacological techniques, the investigators demonstrated that the highly conserved Tyr-267 in the K8 “rod” domain was basally phosphorylated and that its charge was essential for proper filament formation. The authors say, “Our results implicate the rod domain QYE motif tyrosine as an important determinant of IF assembly and solubility properties that can be dynamically modulated by phosphorylation.”
        Figure thumbnail gr1
        Immunofluorescence staining analysis of keratin-transfected NIH-3T3 cells reveals a partially disrupted filament network in the Y267F K8 mutant and abnormal filament aggregation in the Y267D K8 mutant. Scale bars = 20 μm.

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