Gibbs Peter E M, Tudor Cicerone, Maines Mahin D
Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry Rochester, NY, USA.
Front Pharmacol. 2012 Mar 13;3:31. doi: 10.3389/fphar.2012.00031. eCollection 2012.
The expanse of human biliverdin reductase (hBVR) functions in the cells is arguably unmatched by any single protein. hBVR is a Ser/Thr/Tyr-kinase, a scaffold protein, a transcription factor, and an intracellular transporter of gene regulators. hBVR is an upstream activator of the insulin/IGF-1 signaling pathway and of protein kinase C (PKC) kinases in the two major arms of the pathway. In addition, it is the sole means for generating the antioxidant bilirubin-IXα. hBVR is essential for activation of ERK1/2 kinases by upstream MAPKK-MEK and by PKCδ, as well as the nuclear import and export of ERK1/2. Small fragments of hBVR are potent activators and inhibitors of the ERK kinases and PKCs: as such, they suggest the potential application of BVR-based technology in therapeutic settings. Presently, we have reviewed the function of hBVR in cell signaling with an emphasis on regulation of PKCδ activity.
人类胆绿素还原酶（hBVR）在细胞中的广泛功能可以说是任何单一蛋白质都无法比拟的。hBVR是一种丝氨酸/苏氨酸/酪氨酸激酶、一种支架蛋白、一种转录因子，也是基因调节因子的细胞内转运体。hBVR是胰岛素/IGF-1信号通路以及该通路两个主要分支中蛋白激酶C（PKC）激酶的上游激活剂。此外，它是生成抗氧化剂胆红素-IXα的唯一途径。hBVR对于上游MAPKK-MEK和PKCδ激活ERK1/2激酶以及ERK1/2的核输入和输出至关重要。hBVR的小片段是ERK激酶和PKC的有效激活剂和抑制剂：因此，它们表明基于BVR的技术在治疗环境中的潜在应用。目前，我们综述了hBVR在细胞信号传导中的功能，重点是PKCδ活性的调节。
