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

Journal

FRONTIERS IN PHARMACOLOGY
Volume 3, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2012.00031

Keywords

biliverdin reductase; protein kinase C; signaling pathways; peptides; biliverdin

Funding

  1. NIH [ES04066, ES12187]

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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-IX alpha. hBVR is essential for activation of ERK1/2 kinases by upstream MAPKK-MEK and by PKC delta, 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 PKCS activity.

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