Mahin D. Maines, Ph.D.

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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.

Current Appointments

• Professor - Department of Biochemistry and Biophysics (SMD)

Education
PhD Pharmacology	Univ of Missouri System Office	1970
MA Biology	Ball State University	1967
BS Biology	Ball State University	1964

Recent Journal Articles
Showing the 5 most recent journal articles. (185 available)
Kapitulnik, J.; Maines, M. D.;. "Pleiotropic functions of biliverdin reductase: cellular signaling and generation of cytoprotective and cytotoxic bilirubin". Trends Pharmacol Sci 30 (2009): 129-137.
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).
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 105 (2008): 6870-5.
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; 282(11):8110-22. Epub 2007 Jan 16.
Lerner-Marmarosh N; Miralem T; Gibbs PE; Maines MD. "Regulation of TNF-alpha-activated PKC-zeta signaling by the human biliverdin reductase: identification of activating and inhibitory domains of the reductase." The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2007; 21(14):3949-62. Epub 2007 Jul 17.