The membrane proximal region of the cytoplasmic domain of the growth hormone receptor is involved in the activation of Stat 3.
Growth hormone receptor (GHR) signaling involves activation of the Janus Kinases (Jak) and of Stat proteins (signal transducers and activators of transcription). Growth hormone (GH) induces transcriptional activation of c-fos gene and the c-sis inducible element (SIE) of its promoter was shown to bind the Stat proteins. Using cells co-transfected with GHR and Stat 3 expression vectors, we directly demonstrate that GH induces tyrosine phosphorylation of Stat 3 and its binding to the SIE probe. We showed, using mutant forms of GHR, that only the cytoplasmic membrane proximal domain of the receptor, including a conserved proline rich region (box 1), is required for this effect.
Sotiropoulos
A
A
INSERM U344, Faculté de Médecine Necker, Paris, France.
Moutoussamy
S
S
Binart
N
N
Kelly
P A
PA
Finidori
J
J
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D006224:Cricetinae; D003593:Cytoplasm / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D015342:DNA Probes; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D013006:Growth Hormone / Q000494:pharmacology; D007700:Kinetics; D008969:Molecular Sequence Data; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000235:genetics; D011986:Receptors, Somatotropin / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor; D017384:Sequence Deletion; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology*; D014162:Transfection
D015342:DNA Probes; D004268:DNA-Binding Proteins; D011986:Receptors, Somatotropin; D050796:STAT3 Transcription Factor; D015534:Trans-Activators; D013006:Growth Hormone; D004247:DNA