The role of GH receptor tyrosine phosphorylation in Stat5 activation
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The role of GH receptor tyrosine phosphorylation in Stat5 activation. / Hansen, J A; Hansen, L H; Wang, X; Kopchick, J J; Gouilleux, F; Groner, B; Møldrup, Annette; Galsgaard, E D; Nielsen, Jens Høiriis; Billestrup, N.
I: Journal of Molecular Endocrinology, Bind 18, Nr. 3, 06.1997, s. 213-21.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - The role of GH receptor tyrosine phosphorylation in Stat5 activation
AU - Hansen, J A
AU - Hansen, L H
AU - Wang, X
AU - Kopchick, J J
AU - Gouilleux, F
AU - Groner, B
AU - Møldrup, Annette
AU - Galsgaard, E D
AU - Nielsen, Jens Høiriis
AU - Billestrup, N
PY - 1997/6
Y1 - 1997/6
N2 - Stimulation of GH receptors leads to rapid activation of Jak2 kinase and subsequent tyrosine phosphorylation of the GH receptor. Three specific tyrosines located in the C-terminal domain of the GH receptor have been identified as being involved in GH-stimulated transcription of the Spi 2.1 promoter. Mutated GH receptors lacking all but one of these three tyrosines are able to mediate a transcriptional response when transiently transfected into CHO cells together with a Spi 2.1 promoter/luciferase construct. Similarly, these GH receptors were found to be able to mediate activation of Stat5 DNA-binding activity, whereas the GH receptor mutant lacking all intracellular tyrosines was not. Synthetic tyrosine phosphorylated peptides corresponding to the GH receptor sequence around the three tyrosines inhibited Stat5 DNA-binding activity while their non-phosphorylated counterparts were ineffective. Tyrosine phosphorylated GST-GH receptor fusion proteins specifically bound to Stat5 in extracts from COS 7 cells transfected with Stat5 cDNA. This binding could be inhibited by tyrosine phosphorylated peptides derived from the GH receptor. This study thus demonstrated that specific GH receptor tyrosine residues, in their phosphorylated state, are involved in transcriptional signaling by directly interacting with Stat5.
AB - Stimulation of GH receptors leads to rapid activation of Jak2 kinase and subsequent tyrosine phosphorylation of the GH receptor. Three specific tyrosines located in the C-terminal domain of the GH receptor have been identified as being involved in GH-stimulated transcription of the Spi 2.1 promoter. Mutated GH receptors lacking all but one of these three tyrosines are able to mediate a transcriptional response when transiently transfected into CHO cells together with a Spi 2.1 promoter/luciferase construct. Similarly, these GH receptors were found to be able to mediate activation of Stat5 DNA-binding activity, whereas the GH receptor mutant lacking all intracellular tyrosines was not. Synthetic tyrosine phosphorylated peptides corresponding to the GH receptor sequence around the three tyrosines inhibited Stat5 DNA-binding activity while their non-phosphorylated counterparts were ineffective. Tyrosine phosphorylated GST-GH receptor fusion proteins specifically bound to Stat5 in extracts from COS 7 cells transfected with Stat5 cDNA. This binding could be inhibited by tyrosine phosphorylated peptides derived from the GH receptor. This study thus demonstrated that specific GH receptor tyrosine residues, in their phosphorylated state, are involved in transcriptional signaling by directly interacting with Stat5.
KW - Amino Acid Sequence
KW - Animals
KW - Base Sequence
KW - CHO Cells
KW - COS Cells
KW - Cricetinae
KW - DNA, Complementary
KW - DNA-Binding Proteins
KW - Milk Proteins
KW - Phosphorylation
KW - Plasmids
KW - Receptors, Somatotropin
KW - Recombinant Fusion Proteins
KW - STAT5 Transcription Factor
KW - Trans-Activators
KW - Transcription, Genetic
KW - Transfection
KW - Tyrosine
M3 - Journal article
C2 - 9195475
VL - 18
SP - 213
EP - 221
JO - Journal of Molecular Endocrinology
JF - Journal of Molecular Endocrinology
SN - 0952-5041
IS - 3
ER -
ID: 47972945