@article{17a11cd2896d432584b356f8803546f6,
title = "Secreted phosphoprotein 1 binds integrins to initiate multiple cell signaling pathways, including FRAP1/mTOR, to support attachment and force-generated migration of trophectoderm cells",
abstract = "Attachment and migration of trophectoderm (Tr) cells, hallmarks of blastocyst implantation in mammals, are unique uterine events. Secreted phosphoprotein 1 (SPP1) in the uterus binds integrins on conceptus Tr and uterine luminal epithelium (LE), affecting cell-cell and cell-matrix interactions. The signal transduction pathways activated by SPP1 and integrins in conceptuses have not been elucidated. Results of this study demonstrate that SPP1 binds αvβ3 and α5β1 integrins to induce focal adhesion assembly, a prerequisite for adhesion and migration of Tr, through activation of: 1) P70S6K via crosstalk between FRAP1/mTOR and MAPK pathways; 2) mTOR, PI3K, MAPK3/MAPK1 (Erk1/2) and MAPK14 (p38) signaling to stimulate Tr cell migration; and 3) focal adhesion assembly and myosin II motor activity to induce migration of Tr cells. These cell signaling pathways, acting in concert, mediate adhesion, migration and cytoskeletal remodeling of Tr cells essential for expansion and elongation of conceptuses and attachment to uterine LE for implantation.",
keywords = "Implantation, Integrins, MTOR, Mitogen activated protein kinases, Secreted phosphoprotein 1, Trophectoderm",
author = "Jinyoung Kim and Erikson, {David W.} and Burghardt, {Robert C.} and Spencer, {Thomas E.} and Guoyao Wu and Bayless, {Kayla J.} and Johnson, {Greg A.} and Bazer, {Fuller W.}",
note = "Funding Information: The authors thank Dr. Gwonhwa Song for performing p-RPS6 immunohistochemistry and Mr. James W. Frank for performing alpha-actinin immunofluorescence to localize these proteins in ovine trophectoderm in vivo, and Dr. Magnus H{\"o}{\"o}k of the Institute of Biosciences and Technology, Texas A&M Health Science Center for providing recombinant wild-type and mutant rat SPP1 His-tagged expression vectors. This project was supported by National Research Initiative Competitive Grant nos. 2006-35203-17283 (F.W.B.) and 2006-35203-17199 (G.A.J.) from the USDA Cooperative State Research, Education and Extension service . This research was also supported by the WCU (World Class University) program ( R31-10056 ) through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology . Microscopy analysis was performed in the Texas A&M College of Veterinary Medicine Image Analysis Laboratory which has been supported in part by NIH grants S10RR022532 , P42ES004917 and P30ES009106 .",
year = "2010",
month = jun,
doi = "10.1016/j.matbio.2010.04.001",
language = "English (US)",
volume = "29",
pages = "369--382",
journal = "Matrix Biology",
issn = "0945-053X",
publisher = "Elsevier",
number = "5",
}