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.
Biliverdin Reductase is a Novel Cell Proliferation and Differentiation Factor
United States Serial NO.: 10/045,545
Filed Date: January 14, 2002
Title: Methods of Modifying Cell Structure and Remodeling Tissue
Invented by: Mahin Maines
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Biliverdin Reductase is a Novel Cell Proliferation and Differentiation Factor
United States Serial NO.: 11/205,562
Filed Date: August 17, 2005
Title: Methods of Modifying Cell Structure and Remodeling Tissue
Invented by: Mahin Maines
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Human Biliverdin Reductase is a New Member of the Insulin Receptor Substrate Family with Serine/Threonine/Tyrosine Kinase Activity
United States Serial NO.: 11/816,557
Filed Date: February 21, 2006
Title: Methods of Modifying Insulin Signaling Using Biliverdin Reductase
Invented by: Mahin Maines
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Trans-activation of the Human Biliverdin Rreductase and Protein Kinase C-delta: a Fragment of hBVR and Its Activity Product Are Potent Inhibitors of the PKC
United States Serial NO.: 12/941,883
Filed Date: November 8, 2010
Title: Use of Human Biliverdin Reductase and Fragments Thereof for the Treatment of Protein Kinase C-Delta and ERK Related Conditions
Invented by: Mahin Maines
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Human Biliverdin Reductase-Based Peptides and their Potential Role in Treating Diabetes and Hypoglycemia
United States Serial NO.: 13/976,825
Filed Date: December 28, 2011
Title: Methods of Modifying Insulin Signaling Using Biliverdin Reductase (BVR) and BVR Derived Peptides
Invented by: Mahin Maines
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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." FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2010 Sep; 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. Link |
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; . Link |
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. Link |
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. |
