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However, the mechanisms underlying uterine remodeling are largely unknown. Protein kinases and phosphatases play critical roles in regulating the phosphorylation of proteins involved in the smooth muscle cell functions. In the present study, we found that Src-homology phosphatase type-1 (SHP-1, PTPN6) was significantly decreased in human myometrium in labor compared with that not in labor. Timed-pregnant mice injected intraperitoneally with the specific SHP-1 inhibitor protein tyrosine phosphatase inhibitor I (PTPI-1) manifested significantly preterm labor, with enriched plasmalemmal dense plaques between myometrial cells and increased phosphorylation at Tyr397 and Tyr576\/577 sites of focal adhesion kinase (FAK) in myometrial cells, which remained to the time of labor, whereas the phosphorylation levels of ERK1\/2 and phosphatidylinositol 3 kinase (PI3K) showed a rapid increase upon PTPI-1 injection but fell back to normal at the time of labor. The Tyr576\/577 in FAK played an important role in the interaction between FAK and SHP-1. Knockdown of SHP-1 dramatically increased the spontaneous contraction of human uterine smooth muscle cells (HUSMCs), which was reversed by coinfection of a FAK-knockdown lentivirus. PGF<jats:sub>2\u03b1 <\/jats:sub>downregulated SHP-1 via PLC\u03b2-PKC-NF-\u03baB or PI3K-NF-\u03baB pathways, suggesting the regenerative downregulation of SHP-1 enhances the uterine remodeling and plasticity by activating FAK and subsequent focal adhesion pathway, which eventually facilitates myometrium contraction and leads to labor. The study sheds new light on understanding of mechanisms that underlie the initiation of labor, and interventions for modulation of SHP-1 may provide a potential strategy for preventing preterm birth. <\/jats:p>","DOI":"10.1152\/ajpendo.00068.2020","type":"journal-article","created":{"date-parts":[[2020,4,28]],"date-time":"2020-04-28T19:48:21Z","timestamp":1588103301000},"page":"E930-E942","source":"Crossref","is-referenced-by-count":9,"title":["Decrease in SHP-1 enhances myometrium remodeling via FAK activation leading to labor"],"prefix":"10.1152","volume":"318","author":[{"given":"Huai-Yan","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Physiology, Second Military Medical University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling-Tong","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Physiology, Second Military Medical University, Shanghai, 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