Research Bio
The protein kinases mediate eukaryotic cells' response to internal and external stimuli such as a growth and differentiation factors, hormones, drugs and chemicals. The cell signaling pathways that transduce stimuli depend on cascades of phosphorylation /dephosphorylation events and kinase activities. The heme metabolic pathway, which converts, sequentially, heme to biliverdin plus CO, and bilirubin, reflects activities of heme oxygenase (HO) isozymes 1,2and 3, which constitute the HSP32 (heat shock/stress protein) family of proteins, and biliverdin reductase (BVR). Our recent studies have identified the heme metabolic pathway as a component of the cell signal transduction pathways.
We have described CO as a signaling molecule; HO proteins as an intracellular sink for NO and potentially an intracellular oxygen sensor, bilirubin and biliverdin as modulators of protein phosphorylation. We have recently described biliverdin reductase as a new member of the dual specificity kinase (serine/threonine/tyrosine kinase) family, a leucine zipper-type transcription factor for cAMP and AP-1 regulated genes and an inhibitor of apoptosis. We are further investigating how the HO/BVR pathway modulates cell signaling and cell cycle processes.
2010 Sep
Gibbs PE, Miralem T, Maines MD. "Characterization of the human biliverdin reductase gene structure and regulatory elements: promoter activity is enhanced by hypoxia and suppressed by TNF-alpha-activated NF-kappaB." The FASEB journal : official publication of the Federation of
American Societies for Experimental Biology. 2010 Sep 0; 24(9):3239-54. Epub 2010 Apr 21. |
2009
Kapitulnik, J.; Maines, M. D.;. "Pleiotropic functions of biliverdin reductase: cellular signaling and generation of cytoprotective and cytotoxic bilirubin". Trends Pharmacol Sci. 2009; 30(33): 129-137. |
2008
Tudor, C.; Lerner-Marmarosh, N.; Engelborghs, Y.; Gibbs, P. E.; Maines, M. D.;. "Biliverdin reductase is a transporter of heme into the nucleus and is essential to regulation of HO-1 gene expression by hematin". Biochem J. 2008; . |
2008
Lerner-Marmarosh, N.; Miralem, T.; Gibbs, P. E.; Maines, M. D.;. "Human biliverdin reductase is an ERK activator; hBVR is an ERK nuclear transporter and is required for MAPK signaling". Proc Natl Acad Sci U S A. 2008; 105(319): 6870-5. |
2007 Mar 16
Maines MD, Miralem T, Lerner-Marmarosh N, Shen J, Gibbs PE. "Human biliverdin reductase, a previously unknown activator of protein kinase C betaII." The Journal of biological chemistry. 2007 Mar 16; 282(11):8110-22. Epub 2007 Jan 16. |
