The biologic actions of parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHrP) are mediated through a common PTH/PTHrP receptor. Down-regulation and desensitization of the PTH/PTHrP receptor is an important process in PTH/PTHrP receptor physiology. Binding of PTH or PTHrP to its receptor results in receptor phosphorylation, internalization, desensitization, recycling and or degradation. Internalization of the PTH/PTHrP receptor may lead to desensitization and/or re-sensitization of the PTH and PTHrP responses and/or downregulation and degradation of the receptor. In this project I will use cell lines, stably expressing a green fluorescent protein (GFP) tagged PTH/PTHrP receptor, to examine the hypotheses that 1) activation of the PTH/PTHrP receptor is required for internalization, 2) PTH-induced phosphorylation is required for internalization and 3) that internalization may have an important role in PTH/PTHrP receptor signaling through adenylate cyclase, phospholipase C, calcium and/or MAP kinase.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DK010087-03
Application #
6516938
Study Section
General Medicine B Study Section (GMB)
Program Officer
Hyde, James F
Project Start
2002-04-01
Project End
Budget Start
2002-04-01
Budget End
2003-03-31
Support Year
3
Fiscal Year
2002
Total Cost
$54,352
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
Tawfeek, Hesham A W; Abou-Samra, Abdul B (2004) Important role for the V-type H(+)-ATPase and the Golgi apparatus in the recycling of PTH/PTHrP receptor. Am J Physiol Endocrinol Metab 286:E704-10
Tawfeek, Hesham A W; Qian, Fang; Abou-Samra, Abdul B (2002) Phosphorylation of the receptor for PTH and PTHrP is required for internalization and regulates receptor signaling. Mol Endocrinol 16:1-13
Tawfeek, H A; Che, J; Qian, F et al. (2001) Parathyroid hormone receptor internalization is independent of protein kinase A and phospholipase C activation. Am J Physiol Endocrinol Metab 281:E545-57