期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 192, 期 6, 页码 835-845出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.192.6.835
关键词
vitamin A; redox regulation; protein kinase C; Raf kinase; retinoid receptors
资金
- NCI NIH HHS [F32 CA069718, R01 CA049933, CA49933, CA69718] Funding Source: Medline
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 alpha, delta, zeta, and mu, 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 PKC alpha 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.
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