An IGF1/insulin receptor substrate-1 pathway stimulates a mitotic kinase (cdk1) in the uterine epithelium during the proliferative response to estradiol.

ABSTRACT: Estrogens are potent mitogens for some target organs, such as the uterus, and cancers that develop in this organ might be linked to the proliferative action of these hormones. However, the mechanism by which estrogens influence the cell cycle machinery is not known. We found that a null mutation for the insulin receptor substrate (IRS)-1, a docking protein that is important for IGF1 signaling, compromised hormone-induced mitosis in the uterine epithelium; BrdU incorporation was not affected. This selective effect on mitosis was associated with a reduction in uterine cyclin B-associated kinase activity; cyclin A-associated kinase activity was not changed. The null mutation also reduced the extent of hormone-induced phosphorylation of endogenous uterine histone H1, as determined with phospho

SUBMITTER: Walker MP 

PROVIDER: S-EPMC4766979 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature