Redig Amanda J, Sassano Antonella, Majchrzak-Kita Beata, Katsoulidis Efstratios, Liu Hui, Altman Jessica K, Fish Eleanor N, Wickrema Amittha, Platanias Leonidas C
Robert H. Lurie Comprehensive Cancer Center and Division of Hematology/Oncology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
J Biol Chem. 2009 Apr 17;284(16):10301-14. doi: 10.1074/jbc.M807254200. Epub 2009 Feb 11.
Type I interferons (IFNs) are cytokines with diverse biological properties, including antiviral, growth inhibitory, and immunomodulatory effects. Although several signaling pathways are activated during engagement of the type I IFN receptor and participate in the induction of IFN responses, the mechanisms of generation of specific signals for distinct biological effects remain to be elucidated. We provide evidence that a novel member of the protein kinase C (PKC) family of proteins is rapidly phosphorylated and activated during engagement of the type I IFN receptor. In contrast to other members of the PKC family that are also regulated by IFN receptors, PKCeta does not regulate IFN-inducible transcription of interferon-stimulated genes or generation of antiviral responses. However, its function promotes cell cycle arrest and is essential for the generation of the suppressive effects of IFNalpha on normal and leukemic human myeloid (colony-forming unit-granulocyte macrophage) bone marrow progenitors. Altogether, our studies establish PKCeta as a unique element in IFN signaling that plays a key and essential role in the generation of the regulatory effects of type I IFNs on normal and leukemic hematopoiesis.
I型干扰素（IFN）是一类具有多种生物学特性的细胞因子，包括抗病毒、生长抑制和免疫调节作用。虽然在I型干扰素受体结合过程中会激活多种信号通路并参与IFN反应的诱导，但产生不同生物学效应的特定信号的生成机制仍有待阐明。我们提供的证据表明，蛋白激酶C（PKC）家族的一个新成员在I型干扰素受体结合过程中会迅速磷酸化并被激活。与同样受IFN受体调节的PKC家族其他成员不同，PKCε并不调节干扰素刺激基因的IFN诱导转录或抗病毒反应的产生。然而，它的功能促进细胞周期停滞，并且对于IFNα对正常和白血病人类髓系（集落形成单位 - 粒细胞巨噬细胞）骨髓祖细胞产生抑制作用至关重要。总之，我们的研究确定PKCε是IFN信号传导中的一个独特元件，在I型干扰素对正常和白血病造血的调节作用的产生中起关键且必不可少的作用。
