Thyrotropin-releasing hormone-stimulated thyrotropin expression involves islet-brain-1/c-Jun N-terminal kinase interacting protein-1.
Islet-brain-1 (IB1)/c-Jun N-terminal kinase interacting protein 1 (JIP-1) is a scaffold protein that is expressed at high levels in neurons and the endocrine pancreas. IB1/JIP-1 interacts with the c-Jun N-terminal kinase and mediates the specific physiological stimuli (such as cytokines). However, the potential role of the protein in the pituitary has not been evaluated. Herein, we examined expression of the gene encoding IB1/JIP-1 and its translated product in the anterior pituitary gland and a pituitary cell line, GH3. We then examined the potential role of IB1/JIP-1 in controlling TSH-beta gene expression. Exposure of GH3 cells to TRH stimulated the expression of IB1/JIP-1 protein levels, mRNA, and transcription of the promoter. The increase of IB1/JIP-1 content by transient transfection study of a vector encoding IB1/JIP-1 or by the stimulation of TRH stimulates TSH-beta promoter activity. This effect is not found in the presence of a mutated nonfunctional (IB1S59N) IB1/JIP-1 protein. Together, these facts point to a central role of the IB1/JIP-1 protein in the control of TRH-mediated TSH-beta stimulation.
Abe
Hiroshi
H
First Department of Internal Medicine, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan.
Murao
Koji
K
Imachi
Hitomi
H
Cao
Wen M
WM
Yu
Xiao
X
Yoshida
Kazuya
K
Wong
Norman C W
NC
Shupnik
Margaret A
MA
Haefliger
Jacques-Antoine
JA
Waeber
Gérard
G
Ishida
Toshihiko
T
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D002461:Cell Line, Transformed; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D016296:Mutagenesis; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000502:physiology*; D051381:Rats; D037322:Thyrotropin, beta Subunit / Q000235:genetics*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; C110528:Mapk8ip1 protein, rat; D037322:Thyrotropin, beta Subunit; D013973:Thyrotropin-Releasing Hormone