Abstract

Angiotensin II can act as a growth and differentiation factor for both smooth muscle and renal cells. While the biochemistry of the traditional effects of angiotensin II are understood in some detail, the biochemical actions of angiotensin II leading to growth regulation are far less clear. This grant adopts the hypothesis that to understand angiotensin II-mediated cell growth and differentiation, it is critical to study the intracellular signaling events initiated when angiotensin II binds to the AT 1 receptor. One such pathway is the Jak kinases and STAT transcription factors. My group has made an important contribution in describing the activation of this pathway by the AT 1 receptor. We propose to continue these studies by dissecting the binding of the At1 receptor with Jak2 kinase (Specific Aim 1) and with Stat1 (Specific Aim 2). We postulate that a critical region of the AT1 receptor is the signaling motif YIPP found in the carboxy terminal tail of the receptor, and that t his motif is necessary for angiotensin II- mediated Jak-STAT activation.
Specific Aim 3 is to investigate the role of the YIPP motif in non-STAT signaling. The final portion of the grant is to study the role of the Jak-STATpathway in angiotensin II dependent cell proliferation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37DK039777-13
Application #
6177032
Study Section
Cardiovascular and Renal Study Section (CVB)
Program Officer
Hirschman, Gladys H
Project Start
1988-04-01
Project End
2002-08-31
Budget Start
2000-09-01
Budget End
2001-08-31
Support Year
13
Fiscal Year
2000
Total Cost
$256,416
Indirect Cost

  Institution

Name
Emory University
Department
Pathology
Type
Schools of Medicine
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322

  Publications

Iravanian, Shahriar; Sovari, Ali A; Lardin, Harvey A et al. (2011) Inhibition of renin-angiotensin system (RAS) reduces ventricular tachycardia risk by altering connexin43. J Mol Med (Berl) 89:677-87
Shen, Xiao Z; Xiao, Hong D; Li, Ping et al. (2008) Tissue specific expression of angiotensin converting enzyme: a new way to study an old friend. Int Immunopharmacol 8:171-6
Shen, Xiao Z; Li, Ping; Weiss, Daiana et al. (2007) Mice with enhanced macrophage angiotensin-converting enzyme are resistant to melanoma. Am J Pathol 170:2122-34
Kasi, Vijaykumar S; Xiao, Hong D; Shang, Lijuan L et al. (2007) Cardiac-restricted angiotensin-converting enzyme overexpression causes conduction defects and connexin dysregulation. Am J Physiol Heart Circ Physiol 293:H182-92
Reudelhuber, Timothy L; Bernstein, Kenneth E; Delafontaine, Patrick (2007) Is angiotensin II a direct mediator of left ventricular hypertrophy? Time for another look. Hypertension 49:1196-201
Bernstein, Kenneth E (2006) Views of the renin-angiotensin system: brilling, mimsy, and slithy tove. Hypertension 47:509-14
Fuchs, Sebastien; Frenzel, Kristen; Hubert, Christine et al. (2005) Male fertility is dependent on dipeptidase activity of testis ACE. Nat Med 11:1140-2; author reply 1142-3
Gletsu, Nana; Doan, Thanh N; Cole, Justin et al. (2005) Angiotensin II-induced hypertension in mice caused an increase in insulin secretion. Vascul Pharmacol 42:83-92
Bernstein, Kenneth E; Xiao, Hong D; Frenzel, Kristen et al. (2005) Six truisms concerning ACE and the renin-angiotensin system educed from the genetic analysis of mice. Circ Res 96:1135-44
Hashimoto, Seiji; Adams, Jon W; Bernstein, Kenneth E et al. (2005) Micropuncture determination of nephron function in mice without tissue angiotensin-converting enzyme. Am J Physiol Renal Physiol 288:F445-52

Showing the most recent 10 out of 59 publications