FEMALE REPRODUCTIVE TRACT - B
Wednesday, August 4, 2004
10:30 AM–12:30 PM
(802) DIFFERENTIAL EXPRESSION OF PROTEIN KINASE A, AKAP79, AND PP2B IN PREGNANT HUMAN MYOMETRIAL PLASMA MEMBRANE PRIOR TO AND DURING LABOR.
Ku, Chun-Ying1, Word, Ruth2, Sanborn, Barbara1, 1 Colorado State University, Fort Collins, CO2 Univ. of Texas Southwestern Medical Center, Dallas, TX
ABSTRACT- The molecular mechanisms that mediate the onset of labor in human remain unclear. We have previously shown that the association of protein kinase A (PKA) with purified myometrial plasma membrane declined by the end of pregnancy in the rat. Coincident with the decline in membrane-associated PKA, the ability of 8-(4-chlorophenylthio)-cAMP (CPT-cAMP) to inhibit oxytocin-stimulated phosphatidylinositide turnover diminished markedly between Days 19 and 21 of gestation in the pregnant rat myometrium. To determine if similar changes occur in human myometrium near term, we examined the expression of PKA catalytic subunit (PKA-cat), PKA regulatory subunit (PKA-reg), A-kinase anchoring protein (AKAP79), protein phosphatase (PP2B) and Gq in not-in-labor (NIL, n=7-14) and in-labor (IN, n=7-14) pregnant human myometrial plasma membrane obtained from cesarean sections. PKA-reg, PKA-cat, AKAP79 and PP2B concentrations, expressed relative to caveolin-1 (invariant marker) declined by 18, 10, 15 and 32% (P<0.05, n=12-14) respectively, in IL myometrial plasma membrane. In contrast, Gq/caveolin-1 exhibited no change. AKAP79 co-precipitated with PP2B, consistent with the association of these proteins. These data show that, while PKA and PP2B are found in human myometrial plasma membrane along with AKAP79, the decline between NIL and IL samples is less pronounced between these intervals than during late pregnancy in the rat. Whether these changes occur earlier in the human and whether such changes affect negative feedback on contractant signaling in human myometrium remain to be determined. Supported by HD09618
KEY WORDS: AKAP79, PKA, human myometrial, PP2B