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

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.