Abstract

Protein kinase Cs (PKC) are a ubiquitous family of regulatory enzymes that associate with membranes and are activated by diacyloglycerol or tumor promoting agonists such as phorbol esters. These lipophilic activators bind to conserved cysteine-rich domains. We have determined the crystal structure of the second cysteine-rich activator binding domain, known as 'cys2', of PXC delta by multiwavelength anomalous dispersion from native zinc ions. We have also determined the structure of the cys2 domain complex with the tumor promoting PKC activator phorbol ester. The structure explains the roles of phorbol esters and the cysteine-rich domain in the activation and membrane insertion of PKC.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Intramural Research (Z01)
Project #
1Z01DK036118-02
Application #
5201990
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1995
Total Cost
Indirect Cost

  Institution

Name
National Institute of Diabetes and Digestive and Kidney Diseases
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Yadav, Umesh C S; Srivastava, Satish K; Ramana, Kota V (2012) Prevention of VEGF-induced growth and tube formation in human retinal endothelial cells by aldose reductase inhibition. J Diabetes Complications 26:369-77
Kalariya, Nilesh M; Shoeb, Mohammad; Ansari, Naseem H et al. (2012) Antidiabetic drug metformin suppresses endotoxin-induced uveitis in rats. Invest Ophthalmol Vis Sci 53:3431-40
Pandey, Saumya; Srivastava, Satish K; Ramana, Kota V (2012) A potential therapeutic role for aldose reductase inhibitors in the treatment of endotoxin-related inflammatory diseases. Expert Opin Investig Drugs 21:329-39
Shoeb, Mohammad; Yadav, Umesh C S; Srivastava, Satish K et al. (2011) Inhibition of aldose reductase prevents endotoxin-induced inflammation by regulating the arachidonic acid pathway in murine macrophages. Free Radic Biol Med 51:1686-96
Tammali, Ravinder; Saxena, Ashish; Srivastava, Satish K et al. (2011) Aldose reductase inhibition prevents hypoxia-induced increase in hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) by regulating 26 S proteasome-mediated protein degradation in human colon cancer cells. J Biol Chem 286:24089-100
Srivastava, Satish K; Yadav, Umesh C S; Reddy, Aramati B M et al. (2011) Aldose reductase inhibition suppresses oxidative stress-induced inflammatory disorders. Chem Biol Interact 191:330-8
Reddy, Aramati B M; Tammali, Ravinder; Mishra, Rakesh et al. (2011) Aldose reductase deficiency protects sugar-induced lens opacification in rats. Chem Biol Interact 191:346-50
Yadav, Umesh C S; Shoeb, Mohammad; Srivastava, Satish K et al. (2011) Amelioration of experimental autoimmune uveoretinitis by aldose reductase inhibition in Lewis rats. Invest Ophthalmol Vis Sci 52:8033-41
Tammali, Ravinder; Srivastava, Satish K; Ramana, Kota V (2011) Targeting aldose reductase for the treatment of cancer. Curr Cancer Drug Targets 11:560-71
Yadav, Umesh C S; Shoeb, Mohammed; Srivastava, Satish K et al. (2011) Aldose reductase deficiency protects from autoimmune- and endotoxin-induced uveitis in mice. Invest Ophthalmol Vis Sci 52:8076-85

Showing the most recent 10 out of 67 publications