Progesterone receptor contains a proline-rich motif that directly interacts with SH3 domains and activates c-Src family tyrosine kinases.

Abstract:

:Steroid hormones have rapid nongenomic effects on cell-signaling pathways, but the receptor mechanisms responsible for this are not understood. We have identified a specific polyproline motif in the amino-terminal domain of conventional progesterone receptor (PR) that mediates direct progestin-dependent interaction of PR with SH3 domains of various cytoplasmic signaling molecules, including c-Src tyrosine kinases. Through this interaction, PR is a potent activator of Src kinases working by an SH3 domain displacement mechanism. By mutagenesis, we also show that rapid progestin-induced activation of Src and downstream MAP kinase in mammalian cells is dependent on PR-SH3 domain interaction, but not on the transcriptional activity of PR. Preliminary evidence for the biological significance of this PR signaling pathway through regulatory SH3 domains was shown with respect to an influence on progestin-induced growth arrest of breast epithelial cells and induction of Xenopus oocyte maturation.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Boonyaratanakornkit V,Scott MP,Ribon V,Sherman L,Anderson SM,Maller JL,Miller WT,Edwards DP

doi

10.1016/s1097-2765(01)00304-5

subject

Has Abstract

pub_date

2001-08-01 00:00:00

pages

269-80

issue

2

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(01)00304-5

journal_volume

8

pub_type

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