Relaxin activates the MAP kinase pathway in human endometrial stromal cells

The reproductive hormone, relaxin, is structurally similar to insulin and insulin‐like growth factor (IGF). Although a number of cellular responses to relaxin have been described, intracellular signaling mechanisms that link relaxin receptor engagement to alterations in gene expression remain unchar...

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Bibliographic Details
Published in:Journal of cellular biochemistry 2002, Vol.85 (3), p.536-544
Main Authors: Zhang, Qiang, Liu, Shu-Hui, Erikson, Mark, Lewis, Martyn, Unemori, Elaine
Format: Article
Language:English
Subjects:
Cells, Cultured
Cyclic AMP Response Element-Binding Protein - drug effects
Cyclic AMP Response Element-Binding Protein - metabolism
endometrial cells
Endometrium - cytology
Endometrium - metabolism
Endothelial Growth Factors - genetics
Enzyme Activation - drug effects
Enzyme Inhibitors - pharmacology
Female
Humans
Intercellular Signaling Peptides and Proteins - genetics
JNK Mitogen-Activated Protein Kinases
Leukemia - metabolism
Lymphokines - drug effects
Lymphokines - genetics
MAP kinase
MAP Kinase Kinase Kinase 1
MAP Kinase Signaling System - physiology
Mitogen-Activated Protein Kinases - drug effects
Mitogen-Activated Protein Kinases - metabolism
Monocytes - metabolism
Muscle, Smooth, Vascular - cytology
Muscle, Smooth, Vascular - drug effects
Muscle, Smooth, Vascular - metabolism
Protein-Serine-Threonine Kinases - antagonists & inhibitors
Protein-Serine-Threonine Kinases - metabolism
Proto-Oncogene Proteins - drug effects
Proto-Oncogene Proteins - metabolism
Proto-Oncogene Proteins c-akt
Recombinant Proteins - pharmacology
relaxin
Relaxin - metabolism
Relaxin - pharmacology
signaling
smooth muscle cells
Stromal Cells - metabolism
THP-1 cells
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
VEGF
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Summary:The reproductive hormone, relaxin, is structurally similar to insulin and insulin‐like growth factor (IGF). Although a number of cellular responses to relaxin have been described, intracellular signaling mechanisms that link relaxin receptor engagement to alterations in gene expression remain uncharacterized. In the present study, relaxin treatment of a well‐characterized target, human endometrial stromal cells, resulted in rapid activation of p42/44 mitogen‐activated protein (MAP) kinase, as well as of MAPK (or ERK) kinase (MEK). Using a selective chemical inhibitor of MEK, it was further demonstrated that MEK phosphorylation is critical for relaxin‐induced MAP kinase activation. Relaxin treatment also induced MAP kinase activation in THP‐1 monocytic cells and in human smooth muscle cells, indicating that it may be a major signaling transducer utilized by the relaxin receptor. In contrast to insulin or IGF‐1, relaxin did not trigger the PI 3‐kinase/Akt pathway, perhaps accounting in part for relaxin's unique biological profile. Relaxin was also found to cause activation of the transcription factor CREB, a substrate of the MAP kinase pathway. Finally, activation of the MAP kinase pathway was shown to be essential for optimal stimulation of expression of the gene for vascular endothelial growth factor. J. Cell. Biochem. 85: 536–544, 2002. © 2002 Wiley‐Liss, Inc.
ISSN:0730-2312
1097-4644
DOI:10.1002/jcb.10150