Biliverdin reductase: more than a namesakeThe reductase, its peptide fragments and biliverdin regulate activity of the three classes of protein kinase C.

Abstract

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The expanse of human biliverdin reductase (hBVR) functions in the cells is arguably umatched 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 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.

Keywords

• Peptides
• Protein Kinase C
• Biliverdin Reductase
• Signaling Pathways
• Biliverdin