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(Received for publication, January 3, 1995; and in revised form, April 11, 1995) From the The functional significance of growth hormone (GH) receptor
(GHR) internalization is unknown; therefore, we have analyzed domains
and individual amino acids in the cytoplasmic region of the rat GHR
required for ligand-mediated receptor internalization, receptor
down-regulation, and transcriptional signaling. When various mutated
GHR cDNAs were transfected stably into Chinese hamster ovary cells or
transiently into monkey kidney (COS-7) cells, internalization of the
GHR was found to be dependent upon a domain located between amino acids
318 and 380. Mutational analysis of aromatic residues in this domain
revealed that phenylalanine 346 is required for internalization.
Receptor down-regulation in transiently transfected COS-7 cells was
also dependent upon the phenylalanine 346 residue of the GHR, since no
GH-induced down-regulation was observed in cells expressing the F346A
GHR mutant. In contrast, the ability to stimulate transcription of the
serine protease inhibitor 2.1 promoter by the GHR was not affected by
the phenylalanine 346 to alanine mutation. These results demonstrate
that phenylalanine 346 is essential for GHR internalization and
down-regulation but not for transcriptional signaling, suggesting that
ligand-mediated endocytosis is not a prerequisite for GH-induced gene
transcription.
Volume 270,
Number 29,
Issue of July 21, pp. 17210-17214, 1995
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
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Y. Zhang, R. Guan, J. Jiang, J. J. Kopchick, R. A. Black, G. Baumann, and S. J. Frank Growth Hormone (GH)-induced Dimerization Inhibits Phorbol Ester-stimulated GH Receptor Proteolysis J. Biol. Chem., June 29, 2001; 276(27): 24565 - 24573. [Abstract] [Full Text] [PDF]
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