Membrane-associated serine/threonine protein phosphatase in endometrial cancer.
OBJECTIVE
Reversible serine/threonine protein phosphorylation catalyzed by kinases and phosphatases plays a crucial role in cellular growth and differentiation. We attempted to determine the subcellular location of serine/threonine phosphatase (protein phosphatase type 2A [PP2A]) in endometrial cancer.


METHODS
Endometrial cancers surgically removed were examined. PP2A activity was assessed by measuring the dephosphorylation of phosphopeptide highly selective for the PP2A in cytosol and membranes fractionated on a continuous sucrose density gradient. Its protein level was detected by immunoblotting with a specific antibody.


RESULTS
There were three peaks of PP2A enzyme activity and immunoreactivity corresponding by marker enzyme analysis to the cytoplasm, plasma membrane, and endoplasmic reticulum fractions. An enzyme kinetic analysis showed the different activity in cytosol and plasma membrane; K(m) values of 98+/-12 micromol/L for cytosol and 32+/-6.2 micromol/L for plasma membrane (P<.01), respectively. The membrane phosphatase was sensitive to inhibition by okadaic acid and sodium fluoride, characteristics suggestive of PP2A activity.


CONCLUSIONS
PP2A activity in the plasma membrane of endometrial cancers might be distinct from that present in the cytosol. The plasma membrane PP2A may be responsible for a rapid and initial decrease in intracellular level of phosphoserine and phosphothreonine, interfering with serine/threonine protein phosphorylation-mediated growth of endometrial cancer.
Sugiyama
Michiyo
M
Department of Obstetrics and Gynecology, Gifu University School of Medicine, Tsukasamachi, Gifu 500-8705, Japan.
Imai
Atsushi
A
Furui
Tatsuro
T
Tamaya
Teruhiko
T
D000230:Adenocarcinoma / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D002462:Cell Membrane / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000473:pathology*; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D009367:Neoplasm Staging; D010749:Phosphoprotein Phosphatases / Q000032:analysis / Q000378:metabolism*; D011336:Probability; D012494:Sampling Studies; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor; D010749:Phosphoprotein Phosphatases