Focal adhesion signaling in the rat myometrium is abruptly terminated with the onset of labor.
The dramatic increase in uterine growth during late pregnancy and the generation of labor contractions require dynamic remodeling of myometrial smooth muscle-ECM interactions. In many tissues, such interactions are provided by focal adhesions; however, there are no data as to the expression of focal adhesion proteins or of focal adhesion signaling in the myometrium. In this study, we show that tyrosine phosphorylation of myometrial FAK (FAK-P-Tyr) and of its downstream substrate, paxillin, exhibited a >10-fold increase during late pregnancy (days 15-22 of pregnancy) with each exhibiting a dramatic fall in P-Tyr on day 23 in association with the onset of labor. These changes in FAK-P-Tyr were paralleled by changes in FAK enzyme activity. Activated ERK1 and ERK2 expression remained relatively unchanged from day 15 to day 23, but decreased markedly 1 day post partum. Treatment of late pregnant rats with progesterone prevented the fall in FAK-P-Tyr/enzyme activity on day 23, and also blocked the onset of labor. These data suggest that progesterone (which decreases at term) modulates myometrial FAK activity/focal adhesion signaling and that these changes may underlie the tremendous remodeling that must occur in order for this muscle to develop optimal contractile activity during labor.
Macphee
D J
DJ
Samuel Lunenfeld Research Institute, Department of Obstetrics and Gynaecology, University of Toronto, Mount Sinai Hospital, Ontario, Canada.
Lye
S J
SJ
D000818:Animals; D015153:Blotting, Western; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003599:Cytoskeleton / Q000201:enzymology / Q000502:physiology; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D007150:Immunohistochemistry; D016023:Integrins / Q000096:biosynthesis; D007743:Labor, Obstetric / Q000502:physiology*; D009215:Myometrium / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D051419:Paxillin; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011233:Precipitin Tests; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D011374:Progesterone / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*; D019061:src-Family Kinases / Q000096:biosynthesis
D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D016023:Integrins; D051419:Paxillin; D010750:Phosphoproteins; C496063:Pxn protein, rat; D011374:Progesterone; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496052:Ptk2 protein, rat; D019061:src-Family Kinases