Abstract

We will study three peptidases that cleave biologically active peptides. We will purify kininase I or carboxypeptidase N, the inactivator of bradykinin and anaphylatoxins. We will separate the active subunits of the enzyme, study their substrate specificity, their immunological identity, and the mode of cleavage of the macroenzyme to active subunits by plasma proteases - the inhibition of kininase II or angiotensin I converting enzyme from the kidney and from the gastrointestinal tract will be studied with model inhibitors. The effect of inhibition on function of converting enzyme bound to plasma membrane will also be established - finally, attempts will be made to characterize with model substrates and the site of cleavage of the active peptides will be determined.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL036473-02
Application #
3351512
Study Section
Cardiovascular and Pulmonary Research B Study Section (CVB)
Project Start
1985-09-01
Project End
1988-04-30
Budget Start
1986-12-01
Budget End
1988-04-30
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
University of Illinois at Chicago
Department
Type
Schools of Medicine
DUNS #
121911077
City
Chicago
State
IL
Country
United States
Zip Code
60612

  Publications

Huan, Tianxiao; Joehanes, Roby; Schurmann, Claudia et al. (2016) A whole-blood transcriptome meta-analysis identifies gene expression signatures of cigarette smoking. Hum Mol Genet 25:4611-4623
Lowry, Jessica L; Brovkovych, Viktor; Zhang, Yongkang et al. (2013) Endothelial nitric-oxide synthase activation generates an inducible nitric-oxide synthase-like output of nitric oxide in inflamed endothelium. J Biol Chem 288:4174-93
Zhang, Xianming; Lowry, Jessica L; Brovkovych, Viktor et al. (2012) Characterization of dual agonists for kinin B1 and B2 receptors and their biased activation of B2 receptors. Cell Signal 24:1619-31
Brovkovych, Viktor; Zhang, Yongkang; Brovkovych, Svitlana et al. (2011) A novel pathway for receptor-mediated post-translational activation of inducible nitric oxide synthase. J Cell Mol Med 15:258-69
Erdös, Ervin G; Tan, Fulong; Skidgel, Randal A (2010) Angiotensin I-converting enzyme inhibitors are allosteric enhancers of kinin B1 and B2 receptor function. Hypertension 55:214-20
Skidgel, Randal A; Erdos, Ervin G (2007) Structure and function of human plasma carboxypeptidase N, the anaphylatoxin inactivator. Int Immunopharmacol 7:1888-99
Keil, Cora; Maskos, Klaus; Than, Manuel et al. (2007) Crystal structure of the human carboxypeptidase N (kininase I) catalytic domain. J Mol Biol 366:504-16
Chen, Zhenlong; Deddish, Peter A; Minshall, Richard D et al. (2006) Human ACE and bradykinin B2 receptors form a complex at the plasma membrane. FASEB J 20:2261-70
Stanisavljevic, Sinisa; Ignjatovic, Tatjana; Deddish, Peter A et al. (2006) Angiotensin I-converting enzyme inhibitors block protein kinase C epsilon by activating bradykinin B1 receptors in human endothelial cells. J Pharmacol Exp Ther 316:1153-8
Hecquet, Claudie; Biyashev, Dauren; Tan, Fulong et al. (2006) Positive cooperativity between the thrombin and bradykinin B2 receptors enhances arachidonic acid release. Am J Physiol Heart Circ Physiol 290:H948-58

Showing the most recent 10 out of 77 publications