The cysteine-rich regions of the regulatory domains of Raf and protein kinase C as retinoid receptors Journal Article


Authors: Hoyos, B.; Imam, A.; Chua, R.; Swenson, C.; Tong, G. X.; Levi, E.; Noy, N.; Hämmerling, U.
Article Title: The cysteine-rich regions of the regulatory domains of Raf and protein kinase C as retinoid receptors
Abstract: Vitamin A and its biologically active derivatives, the retinoids, are recognized as key regulators of vertebrate development, cell growth, and differentiation. Although nuclear receptors have held the attention since their discovery a decade ago, we report here on serine/threonine kinases as a new class of retinoid receptors. The conserved cysteine-rich domain of the NH2-terminal regulatory domains of cRaf-1, as well as several select domains of the mammalian protein kinase C (PKC) isoforms α, δ, ζ, and μ, the Drosophila and yeast PKCs, were found to bind retinol with nanomolar affinity. The biological significance was revealed in the alternate redox activation pathway of these kinases. Retinol served as a cofactor to augment the activation of both cRaf and PKCα by reactive oxygen, whereas the classical receptor-mediated pathway was unaffected by the presence or absence of retinol. We propose that bound retinol, owing to its electron transfer capacity, functions as a tag to enable the efficient and directed redox activation of the cRaf and PKC families of kinases.
Keywords: controlled study; protein expression; unclassified drug; raf protein; nonhuman; binding affinity; protein domain; protein analysis; animal cell; mouse; animals; mice; protein binding; drosophila; enzyme activation; protein serine threonine kinase; regulatory mechanism; amino acid sequence; molecular sequence data; kinetics; protein purification; saccharomyces cerevisiae; peptide fragments; glutathione transferase; reactive oxygen metabolite; protein kinase c; binding sites; receptor; retinol; oxidation reduction reaction; retinoid; concentration response; cysteine; isoenzymes; 3t3 cells; proto-oncogene proteins c-raf; raf kinase; vitamin a; retinoids; receptors, retinoic acid; redox regulation; humans; human; priority journal; article; retinoid receptor; retinoid receptors
Journal Title: Journal of Experimental Medicine
Volume: 192
Issue: 6
ISSN: 0022-1007
Publisher: Rockefeller University Press  
Date Published: 2000-09-18
Start Page: 835
End Page: 845
Language: English
DOI: 10.1084/jem.192.6.835
PUBMED: 10993914
PROVIDER: scopus
PMCID: PMC2193291
DOI/URL:
Notes: Export Date: 18 November 2015 -- Source: Scopus
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MSK Authors
  1. Asiya Imam
    3 Imam
  2. Beatrice E Hoyos
    23 Hoyos
  3. Ramon Chua
    21 Chua
  4. Ester Levi
    17 Levi