Abstract

Our goal is to understand how the cellular response to growth hormone is initiated and regulated in target cells. The initiating step in hormone action is binding to membrane receptors. Elucidation of the molecular basis of growth hormone action therefore requires the isolation and purification of this receptor. Growth hormone possesses insulin-like and anti-insulin actions. Growth hormone and insulin each increase the phosphorylation of a protein of Mr 46,000. Pre-exposure to growth hormone decreases the number of insulin receptors on hepatocytes. The role of these processes in potentiating the actions of growth hormone will be characterized. Growth hormone action in cells is regulated by the affinity state of the receptor and the number of receptors on the cell surface. We will characterize the mechanisms that mediate the up- and down-regulation of the growth hormone receptor and determine if a relationship exists between receptor affinity state and receptor activity.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Research Project (R01)
Project #
2R01AM030788-04
Application #
3152129
Study Section
Endocrinology Study Section (END)
Project Start
1982-05-01
Project End
1990-04-30
Budget Start
1985-09-20
Budget End
1986-04-30
Support Year
4
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065

  Publications

Marino, M W; Feld, L J; Jaffe, E A et al. (1991) Phosphorylation of the proto-oncogene product eukaryotic initiation factor 4E is a common cellular response to tumor necrosis factor. J Biol Chem 266:2685-8
Lipson, K E; Kolhatkar, A A; Donner, D B (1989) Alkylation, reduction, solubilization and enrichment of binding activity do not impair the ability of insulin receptors to convert from a rapid- into a slow-dissociating state. Biochem J 259:871-8
Marino, M W; Pfeffer, L M; Guidon Jr, P T et al. (1989) Tumor necrosis factor induces phosphorylation of a 28-kDa mRNA cap-binding protein in human cervical carcinoma cells. Proc Natl Acad Sci U S A 86:8417-21
Lipson, K E; Kolhatkar, A A; Donner, D B (1989) Insulin stimulates proteolysis of the alpha-subunit, but not the beta-subunit, of its receptor at the cell surface in rat liver. Biochem J 261:333-40
Lipson, K E; Kolhatkar, A A; Donner, D B (1988) Cell surface proteolysis and down-regulation of the hepatic insulin receptor. Evidence for selective sorting of intact and degraded receptors after internalization. J Biol Chem 263:10495-501
Lipson, K E; Kolhatkar, A A; Maki, R G et al. (1988) Divalent cations regulate glucagon binding. Evidence for actions on receptor-Ns complexes and on receptors uncoupled from Ns. Biochemistry 27:1111-6
Pfeffer, L M; Stebbing, N; Donner, D B (1987) Cytoskeletal association of human alpha-interferon-receptor complexes in interferon-sensitive and -resistant lymphoblastoid cells. Proc Natl Acad Sci U S A 84:3249-53
Yamada, K; Lipson, K E; Donner, D B (1987) Structure and proteolysis of the growth hormone receptor on rat hepatocytes. Biochemistry 26:4438-43
Yamada, K; Lipson, K E; Marino, M W et al. (1987) Effect of growth hormone on protein phosphorylation in isolated rat hepatocytes. Biochemistry 26:715-21
Yamada, K; Donner, D B (1985) Evidence that non-covalent forces, thiol and disulphide groups affect the structure and binding properties of the prolactin receptor on hepatocytes from pregnant rats. Biochem J 228:383-90