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Focal adhesion signaling is required for myometrial ERK activation and contractile phenotype switch before labor
Author(s) -
Li Yunping,
Gallant Cynthia,
Malek Sabah,
Morgan Kathleen G.
Publication year - 2006
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21033
Subject(s) - focal adhesion , paxillin , myometrium , microbiology and biotechnology , mapk/erk pathway , phosphorylation , proto oncogene tyrosine protein kinase src , contractility , tyrosine phosphorylation , signal transduction , medicine , caldesmon , endocrinology , kinase , chemistry , biology , uterus , calcium , calmodulin
In late pregnancy rapidly increasing fetal growth dramatically increases uterine wall tension. This process has been implicated in the activation of the myometrium for labor, but the mechanisms involved are unclear. Here, we tested, using a rat model, the hypothesis that gestation‐dependent stretch, via activation of focal adhesion signaling, contributes to the published activation of myometrial ERK at the end of pregnancy. Consistent with this hypothesis, we show here that ERK is targeted to adhesion plaques during late pregnancy. Furthermore, myometrial stretch triggers a dramatic increase in myometrial contractility and ERK and caldesmon phosphorylation, confirming the presence of stretch sensitive myometrial signaling element. Screening by anti‐phosphotyrosine immunoblotting for focal adhesion signaling in response to stretch reveals a significant increase in the tyrosine phosphorylated bands identified as focal adhesion kinase (FAK), A‐Raf, paxillin, and Src. Pretreatment with PP2, a Src inhibitor, significantly suppresses the stretch‐induced increases in FAK, paxillin, Src, ERK and caldesmon phosphorylation and myometrial contractility. Thus, focal adhesion‐Src signaling contributes to ERK activation and promotes contraction in late pregnancy. These results point to focal adhesion signaling molecules as potential targets in the modulation of the myometrial contractility and the onset of labor. J. Cell. Biochem. 100: 129–140, 2007. © 2006 Wiley‐Liss, Inc.