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.
Department of Molecular Biology, Genentech, Inc., South San Francisco, California 94080.
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P
Colosi
K
K
Wong
S R
SR
Leong
W I
WI
Wood
D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003001:Cloning, Molecular; D017124:Conserved Sequence; D004247:DNA / Q000096:biosynthesis; D004252:DNA Mutational Analysis; D013006:Growth Hormone / Q000494:pharmacology; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D008969:Molecular Sequence Data; D005810:Multigene Family; D016297:Mutagenesis, Site-Directed; D021382:Protein Sorting Signals / Q000737:chemistry / Q000235:genetics; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000235:genetics; D011986:Receptors, Somatotropin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013936:Thymidine / Q000378:metabolism; D014162:Transfection; D014316:Tritium; D014961:X-Ray Diffraction
D007377:Interleukin-3; D021382:Protein Sorting Signals; D011956:Receptors, Cell Surface; D011986:Receptors, Somatotropin; D011994:Recombinant Proteins; D014316:Tritium; D013006:Growth Hormone; D004247:DNA; D013936:Thymidine