Kamal Mehta

Office Information

464 Hamilton Hall
1645 Neil Ave
Columbus, OH, 43210
Office Phone: (614) 688-8451

Lab Information

Hamilton Hall
1645 Neil Ave
Columbus, OH, 43210

Area of Expertise

Molecular Biology of Lipid Homeostasis

Interest and Subspecialty

The cell signaling pathways that culminate in regulation of low-density lipoprotein (LDL) receptor transcription in response to a variety of extracellular and intracellular signals is the focus of current research. Evidence is accumulating that LDL receptor transcription is under complex regulation and that a major pathway of induction by cytokines, growth factors, and phorbol esters involves the extracellular/mitogen-activated protein kinase (p42/44MAPK) cascade. In fact, degree of p42/44MAPK activation determines the extent of LDL receptor induction. In contrast, LDL receptor expression is under negative control by stress-activated p38MAPK, and suppression of LDL receptor expression by this kinase provides a potential mechanism for stress-induced hypercholesterolemia observed in humans and animals. Endogenous signals, such as cholesterol regulate LDL receptor expression through a different signaling cascade involving protein kinase Ce isoform (PKCe). The ability of cholesterol to directly bind PKCe in an isoform-specific manner strongly supports its role in sensing the cholesterol cellular cholesterol levels. The emerging picture from the above studies is that regulation of LDL receptor transcription results from the activity of a number of interlinked regulatory molecules and pathways, rather than from a single linear events.

Recent Publications

1. Mehta, K. D. (2002) Role of mitogen-activated protein kinases and protein kinase C in regulating low-density lipoprotein receptor expression. Gene Expression 10: 153-164.

2. Mehta, K. D., Radominska-Pandya, A., Kapoor, G. S., Dave, B., and Atkins, B. A. (2002) Critical role of diacylglycerol- and phospholipid-regulated protein kinase Ce in induction of low density lipoprotein receptor transcription in response to depletion of cholesterol. Mol. Cell. Biol. 22(11): 3783-3793.

3. Kapoor, G. S., Atkins, B. A., and Mehta, K. D. (2002) Activation of Raf-1/MEK-1/2/p42/44MAPK cascade is sufficient to uncouple LDL receptor expression from cell growth. Mol. Cell. Biochem. 236: 13-22.

4. Mehta, K. D., and Miller, L. (1999) Stress-activated p38MAPK cascade negatively regulates LDL receptor expression. Trends Cardiovasc. Med. 9(7): 201-205.

5. Singh, R. P., Dhawan, P., Golden, C., Kapoor, G. S., and Mehta, K. D. (1999) One-way cross-talk between p38MAPK and p42/44MAPK: Inhibition of p38MAPK b-isoform induces LDL receptor expression through activation of p42/44MAPK. J. Biol. Chem. 274: 19593-19600.

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