Down-regulation of the mitogen-activated protein kinase cascade immediately before parturition in the rat myometrium.
OBJECTIVE
This study tested the hypothesis that mitogen-activated protein kinase (MAPK) pathway is up-regulated during the course of pregnancy concomitant with uterine hypertrophy.


METHODS
The expression and intracellular distribution of components of the MAPK cascade and the activation of MAPKs erk1 and erk2 were examined in the pregnant rat myometrium (day 10-22 of gestation). Protein expression was detected by Western analysis of myometrial subcellular fractions. Mitogen-activated protein kinase activation was studied by detection of tyrosine phosphorylation of erk1 and erk2 kinases and enzymatic activity.


RESULTS
Mitogen-activated protein kinase activity increased from day 15 to day 20 of pregnancy. Immediately before parturition, MAPK activity, but not expression, declined sharply. During the same interval, membrane expression of the mitogenic-switching protein ras and the ras activator sos declined.


CONCLUSIONS
The shift in intracellular distribution ras and ras chaperone proteins may precede the down-regulation of membrane-dependent mitogenic signaling and uterine hypertrophy as pregnancy approaches parturition.
Ruzycky
A L
AL
Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, Pennsylvania, USA. andre_ruzycky@berlex.com
D000818:Animals; D015153:Blotting, Western; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation; D005260:Female; D020690:GTPase-Activating Proteins; D005865:Gestational Age; D006160:Guanosine Triphosphate / Q000494:pharmacology; D007743:Labor, Obstetric / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D008970:Molecular Weight; D009215:Myometrium / Q000201:enzymology* / Q000648:ultrastructure; D019000:Phosphotyrosine / Q000378:metabolism; D011247:Pregnancy; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020703:ras GTPase-Activating Proteins; D018631:ras Proteins / Q000378:metabolism
D020690:GTPase-Activating Proteins; D011506:Proteins; D020703:ras GTPase-Activating Proteins; D019000:Phosphotyrosine; D006160:Guanosine Triphosphate; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins