Thyrotropin-releasing hormone stimulates phosphorylation of the epidermal growth factor receptor in GH3 pituitary cells.
TRH has been found to stimulate tyrosine phosphorylation of the epidermal growth factor (EGF) receptor. A specific EGF receptor kinase inhibitor, tyrphostin AG1478, substantially reduced TRH-stimulated tyrosine phosphorylation of the EGF receptor. TRH-induced EGF receptor phosphorylation was found to lead to the recruitment of the adapter proteins Grb2 and Shc. TRH treatment also led to phosphorylation of the related receptor tyrosine kinase, HER2. HER2 activation likely contributes to downstream signaling events and enhances EGF receptor action. TRH-induced tyrosine phosphorylation of the EGF receptor was reduced by incubation with a protein kinase C (PKC) kinase inhibitor, GF109203X. EGF receptor phosphorylation was required for full TRH-induced activation of mitogen-activated protein kinase (MAPK) and stimulation of specific transcriptional responses.
Wang
Y H
YH
Department of Cell and Developmental Biology, Oregon Health Sciences University, Portland 97201, USA.
Jue
S F
SF
Maurer
R A
RA
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism*; D017930:Genes, Reporter; D007211:Indoles / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics; D008301:Maleimides / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D010911:Pituitary Neoplasms; D011493:Protein Kinase C / Q000378:metabolism; D011799:Quinazolines; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured; D020032:Tyrphostins / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D011799:Quinazolines; D011994:Recombinant Proteins; D020032:Tyrphostins; C101044:RTKI cpd; D019000:Phosphotyrosine; D013973:Thyrotropin-Releasing Hormone; D008156:Luciferases; D066246:ErbB Receptors; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; C070515:bisindolylmaleimide I