Abstract

Dr. Pestka's overall objective is to elucidate the mechanisms of regulation and function of the interferon gamma receptor. Interferon gamma plays a critical role in the regulation of the immune system and is active on virtually all tissues. The actions of IFN gamma are mediated by its receptor. Dr. Pestka s laboratory and other laboratories have identified two chains of the gamma receptor, gR1 and gR2, that are required for receptor activity and their cDNAs have been cloned. The current proposal focuses on the mechanism of regulation of expression of the gamma receptor, its mechanism of signal transduction, and the elucidation of possibly new biochemical pathways involved in gamma function.
Seven specific aims are proposed as follows: 1. to determine the role of Jak kinases in the specificity of signal transduction; 2. to complement cells lacking Jak kinases with synthetic receptors; 3. to determine the structure and function of the gene for the interferon gR2 chain; 4. to determine the structural requirements for function of the interferon gamma R1 and R2 chains; 5. to delineate other proteins and pathways linked to the interferon gamma receptor; 6. to determine the role of the second interferon gamma receptor chain, gR2, in various responses; and 7. to identify additional accessory factors beyond AF1 (now called gamma R2) involved in the action of gamma interferon.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
3R01CA046465-11S1
Application #
6016758
Study Section
Experimental Virology Study Section (EVR)
Project Start
1988-09-01
Project End
2001-06-30
Budget Start
1998-07-01
Budget End
1999-06-30
Support Year
11
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
University of Medicine & Dentistry of NJ
Department
Genetics
Type
Schools of Medicine
DUNS #
622146454
City
Piscataway
State
NJ
Country
United States
Zip Code
08854

  Publications

Krause, Christopher D; Pestka, Sidney (2007) Historical developments in the research of interferon receptors. Cytokine Growth Factor Rev 18:473-82
Qu, Yongxia; Adler, Victor; Izotova, Lara et al. (2007) The dual-specificity kinases, TOPK and DYRK1A, are critical for oocyte maturation induced by wild-type--but not by oncogenic--ras-p21 protein. Front Biosci 12:5089-97
Krause, Christopher D; Yang, Zhi-Hong; Kim, Young-Sun et al. (2007) Protein arginine methyltransferases: evolution and assessment of their pharmacological and therapeutic potential. Pharmacol Ther 113:50-87
Pestka, Sidney (2007) The interferons: 50 years after their discovery, there is much more to learn. J Biol Chem 282:20047-51
Qu, Yongxia; Adler, Victor; Chu, Tearina et al. (2006) Two dual specificity kinases are preferentially induced by wild-type rather than by oncogenic RAS-P21 in Xenopus oocytes. Front Biosci 11:2420-7
Krause, Christopher D; He, Wen; Kotenko, Sergei et al. (2006) Modulation of the activation of Stat1 by the interferon-gamma receptor complex. Cell Res 16:113-23
Garcia, Carmen S; Curiel, Rafael E; Mwatibo, James M et al. (2006) The antineoplastic agent bryostatin-1 differentially regulates IFN-gamma receptor subunits in monocytic cells: transcriptional and posttranscriptional control of IFN-gamma R2. J Immunol 177:2707-16
Krause, Christopher D; Pestka, Sidney (2005) Evolution of the Class 2 cytokines and receptors, and discovery of new friends and relatives. Pharmacol Ther 106:299-346
Adler, Victor; Qu, Yongxia; Smith, Steven J et al. (2005) Functional interactions of Raf and MEK with Jun-N-terminal kinase (JNK) result in a positive feedback loop on the oncogenic Ras signaling pathway. Biochemistry 44:10784-95
Pestka, Sidney; Krause, Christopher D; Walter, Mark R (2004) Interferons, interferon-like cytokines, and their receptors. Immunol Rev 202:8-32

Showing the most recent 10 out of 84 publications