The proposed studies will examine an alternative model for regulation of the PRL gene.
The specific aims i nclude: 1) Determine the role that the mitogen activated protein kinase (MAPK) pathway plays in mediating the ability of cAMP and thyrotropin releasing hormone (TRH) to stimulate expression of the PRL gene. These studies will involve attempts to block activation of the MAPK pathways. The ability of cAMP and TRH to activate specific MAPK pathways will also be determined.
This aim will test the possibility that a non-receptor tyrosine kinase plays an important role in linking the TRH receptor to the MAPK pathway. A possible role for the Ras superfamily member, Rap1b in mediating cAMP-induced activation of the PRL promoter will also be examined. 2) Explore the mechanisms which permit the LIM-homeodomain transcription factor, mLIM3, to enhance MAPK responsiveness of the PRL gene.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK040339-09
Application #
2016308
Study Section
Endocrinology Study Section (END)
Program Officer
Sato, Sheryl M
Project Start
1988-09-20
Project End
2000-11-30
Budget Start
1996-12-26
Budget End
1997-11-30
Support Year
9
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Oregon Health and Science University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
009584210
City
Portland
State
OR
Country
United States
Zip Code
97239
Howard, Paul W; Jue, Shall F; Maurer, Richard A (2009) Expression of the synaptotagmin I gene is enhanced by binding of the pituitary-specific transcription factor, POU1F1. Mol Endocrinol 23:1563-71
Kievit, Paul; Maurer, Richard A (2005) The pituitary-specific transcription factor, Pit-1, can direct changes in the chromatin structure of the prolactin promoter. Mol Endocrinol 19:138-47
Kievit, P; Lauten, J D; Maurer, R A (2001) Analysis of the role of the mitogen-activated protein kinase in mediating cyclic-adenosine 3',5'-monophosphate effects on prolactin promoter activity. Mol Endocrinol 15:614-24
Howard, P W; Maurer, R A (2001) A point mutation in the LIM domain of Lhx3 reduces activation of the glycoprotein hormone alpha-subunit promoter. J Biol Chem 276:19020-6
Howard, P W; Maurer, R A (2000) Identification of a conserved protein that interacts with specific LIM homeodomain transcription factors. J Biol Chem 275:13336-42
Wang, Y H; Jue, S F; Maurer, R A (2000) Thyrotropin-releasing hormone stimulates phosphorylation of the epidermal growth factor receptor in GH3 pituitary cells. Mol Endocrinol 14:1328-37
Wang, Y H; Maurer, R A (1999) A role for the mitogen-activated protein kinase in mediating the ability of thyrotropin-releasing hormone to stimulate the prolactin promoter. Mol Endocrinol 13:1094-104
Nowakowski, B E; Okimura, Y; Maurer, R A (1997) Characterization of DNA regions mediating the ability of Ca2+/calmodulin dependent protein kinase II to stimulate prolactin promoter activity. Mol Cell Endocrinol 132:109-16
Liang, J; Moye-Rowley, S; Maurer, R A (1995) In vivo mutational analysis of the DNA binding domain of the tissue-specific transcription factor, Pit-1. J Biol Chem 270:25520-5
Howard, P W; Maurer, R A (1995) A composite Ets/Pit-1 binding site in the prolactin gene can mediate transcriptional responses to multiple signal transduction pathways. J Biol Chem 270:20930-6

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