The molecular chaperone Hsp90 is required for signal transduction by wild-type Hck and maintenance of its constitutively active counterpart

G. M. Scholz, S. D. Hartson, K. Cartledge, L. Volk, R. L. Matts, A. R. Dunn

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

We have investigated the relationship between the molecular chaperone heat shock protein-90 (Hsp90) and the signal transducing capacity of the Src-family kinase Hck. Inhibition of Hsp90 with geldanamycin suppressed the ability of bacterial lipopolysaccharide to enhance the cell adhesion properties of macrophages, a phenomenon most likely explained by the reduced expression and activity of Hck in macrophages lacking Hsp90 function. The contribution of Hsp90 to signal transduction by Hck was biochemically dissected further by examining its role in the de novo folding and maintenance of wild-type Hck and its constitutively active counterpart, Hck499F. The folding of nascent wild-type Hck and Hck499F into catalytically active conformations, and their accumulation in cells was found to be dependent on Hsp90 function. Notably, mature Hck499F had a greater requirement for on-going support from Hsp90 than did mature wild-type Hck. This particular finding might have important implications for our understanding of the evolution of oncogenic protein kinases.

Original languageEnglish (US)
Pages (from-to)409-417
Number of pages9
JournalCell Growth and Differentiation
Volume12
Issue number8
StatePublished - Aug 29 2001

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HSP90 Heat-Shock Proteins
Molecular Chaperones
Signal Transduction
Maintenance
Macrophages
src-Family Kinases
Cell Adhesion
Protein Kinases
Lipopolysaccharides

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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The molecular chaperone Hsp90 is required for signal transduction by wild-type Hck and maintenance of its constitutively active counterpart. / Scholz, G. M.; Hartson, S. D.; Cartledge, K.; Volk, L.; Matts, R. L.; Dunn, A. R.

In: Cell Growth and Differentiation, Vol. 12, No. 8, 29.08.2001, p. 409-417.

Research output: Contribution to journalArticle

Scholz, G. M. ; Hartson, S. D. ; Cartledge, K. ; Volk, L. ; Matts, R. L. ; Dunn, A. R. / The molecular chaperone Hsp90 is required for signal transduction by wild-type Hck and maintenance of its constitutively active counterpart. In: Cell Growth and Differentiation. 2001 ; Vol. 12, No. 8. pp. 409-417.
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