Mutational analysis of the intracellular domain of the human growth hormone receptor.

P. Colosi,Ka Wong,S. Leong,William I. Wood

Published 1993 in Journal of Biological Chemistry

ABSTRACT

The human growth hormone (GH) receptor contains an extracellular hormone-binding domain of about 246 amino acids, a single transmembrane domain, and a cytoplasmic region of 350 residues. X-ray crystallographic and functional data show that a single GH molecule dimerizes two receptors to initiate receptor signaling. We have constructed a series of truncations of the cytoplasmic domain of the human GH receptor and have examined the function of these truncated receptors by expressing them in the interleukin-3-dependent promyeloid cell line, FDC-P1. When transfected with a functional GH receptor, these cells grow in the presence of GH without interleukin-3. We find that truncated GH receptors containing as few as 54 amino acids of the cytoplasmic domain are able to transmit a GH proliferative signal; thus, at least 84% of the intracellular domain is unnecessary for signaling in this system. The 54-amino-acid region contains a proline-rich sequence that is found in a similar location in most other members of the GH/cytokine receptor family. Perhaps, this sequence is directly involved in the signaling process mediated by this receptor family.

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