Rational design of potent antagonists to the human growth hormone receptor.
Science
; 256(5064): 1677-80, 1992 Jun 19.
Article
em En
| MEDLINE
| ID: mdl-1535167
A hybrid receptor was constructed that contained the extracellular binding domain of the human growth hormone (hGH) receptor linked to the transmembrane and intracellular domains of the murine granulocyte colony-stimulating factor receptor. Addition of hGH to a myeloid leukemia cell line (FDC-P1) that expressed the hybrid receptor caused proliferation of these cells. The mechanism for signal transduction of the hybrid receptor required dimerization because monoclonal antibodies to the hGH receptor were agonists whereas their monovalent fragments were not. Receptor dimerization occurs sequentially--a receptor binds to site 1 on hGH, and then a second receptor molecule binds to site 2 on hGH. On the basis of this sequential mechanism, which may occur in many other cytokine receptors, inactive hGH analogs were designed that were potent antagonists to hGH-induced cell proliferation. Such antagonists could be useful for treating clinical conditions of hGH excess, such as acromegaly.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores da Somatotropina
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Science
Ano de publicação:
1992
Tipo de documento:
Article
País de publicação:
Estados Unidos