MUTATIONAL ANALYSIS OF THE INTRACELLULAR DOMAIN OF THE HUMAN GROWTH-HORMONE RECEPTOR

The human growth hormone (GH) receptor contains an extracellular hormo ne-binding domain of about 246 amino acids, a single transmembrane dom ain, and a cytoplasmic region of 350 residues. X-ray crystallographic and functional data show that a single GH molecule dimerizes two recep tors to initiate receptor signaling. We have constructed a series of t runcations 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 tra nsfected with a functional GH receptor, these cells grow in the presen ce of GH without interleukin-3. We find that truncated GH receptors co ntaining as few as 54 amino acids of the cytoplasmic domain are able t o transmit a GH proliferative signal; thus, at least 84% of the intrac ellular domain is unnecessary for signaling in this system. The 54-ami no-acid region contains a proline-rich sequence that is found in a sim ilar 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.