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

The cysteine-rich regions of the regulatory domains of Raf and protein kinase C as retinoid receptors.
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DOI:
10.1084/jem.192.6.835
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发表时间:
2000-09-18
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Hämmerling U
Hämmerling U
中科院分区:
其他
文献类型:
--
作者:
Hoyos B;Imam A;Chua R;Swenson C;Tong GX;Levi E;Noy N;Hämmerling U

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维生素A及其生物活性衍生物类维生素A被认为是脊椎动物发育、细胞生长和分化的关键调节因子。尽管核受体自十年前被发现以来一直受到关注,但我们在这里报道了丝氨酸/苏氨酸激酶作为一类新的类视黄醛受体。研究发现,cRaf-1的nh2末端调控域的保守的富含半胱氨酸的结构域,以及哺乳动物蛋白激酶C (PKC)同型体α、δ、ζ和μ的几个选择结构域,果蝇和酵母PKCs,都能以纳米摩尔亲和力结合视黄醇。这些激酶的交替氧化还原激活途径揭示了其生物学意义。视黄醇作为一种辅助因子,通过活性氧增强cRaf和PKCα的激活,而经典的受体介导途径不受视黄醇存在或不存在的影响。我们提出,结合视黄醇由于其电子转移能力,可以作为一种标签,使cRaf和PKC家族的激酶有效和定向氧化还原激活。
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.
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