The DNA repair protein ku is involved in gp130-mediated signal transduction events in PBMC from young but not from elderly subjects

Daniela Frasca, Salvatore Scarpaci, Paola Barattini, Carlo Bartoloni, Luisa Guidi, Mario Costanzo, Gino Doria

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Ku, composed of 70 kDa (ku 70) and 86 kDa (ku 80) proteins, is the DNA-targeting subunit of the DNA-dependent serine/threonine kinase (DNA-PK), which plays a crucial role in DNA double strand break recognition and repair in mammalian cells. We have investigated the effects of an IL-6-type cytokine (K-7/D-6), known to trigger gp130, on the expression and function of the ku protein in cytoplasmic and nuclear extracts of freshly isolated human peripheral blood mononuclear cells (PBMC) from subjects of different ages. DNA-binding of nuclear ku was found to be increased by cytokine treatment of cells from young donors but only to a negligible extent from elderly subjects. This cytokine effect was correlated with a greater amount of phosphorylated ku 80, rather than increased expression of ku 70 and ku 80 proteins. DNA-binding activity of cytoplasmic ku was hardly discernible, as compared to nuclear ku, in both young and elderly subjects and was unaffected by the cytokine treatment regardless of age. Regarding the mechanisms whereby ku and gp130 signaling are coupled in PBMC, results from co-immunoprecipitation experiments have shown that ku in the cytoplasm of PBMC from young, but not from elderly subjects, is associated with Tyk-2, a kinase involved in signal transduction events after gp130 triggering by IL-6-type cytokines. This association was independent of PHA stimulation. Moreover, the present results indicate that after gp130 signaling both Tyk-2 and ku 80 are phosphorylated, suggesting their activation by K-7/D-6.

Original languageEnglish (US)
Pages (from-to)321-328
Number of pages8
JournalExperimental Gerontology
Volume37
Issue number2-3
DOIs
StatePublished - Jan 3 2002
Externally publishedYes

Keywords

  • DNA repair
  • DNA-dependent protein kinase
  • Peripheral blood mononuclear cell
  • Signal transduction

ASJC Scopus subject areas

  • Aging
  • Medicine(all)

Fingerprint Dive into the research topics of 'The DNA repair protein ku is involved in gp130-mediated signal transduction events in PBMC from young but not from elderly subjects'. Together they form a unique fingerprint.

  • Cite this