On the mechanism of activation of protein kinase FA (an activating factor of ATP.Mg-dependent protein phosphatase) in brain myelin.
Protein kinase FA (an activating factor of ATP.Mg-dependent protein phosphatase) has been characterized to exist in two forms in the purified brain myelin. One form of kinase FA is spontaneously active and trypsin-labile, whereas the other form of kinase FA is inactive and trypsin-resistant, suggesting a different membrane topography with active FA exposed on the outer face of the myelin membrane and inactive FA buried within the myelin membrane. When myelin was solubilized in 1% Triton X-100, all kinase FA became active and trypsin-labile. Phospholipid reconstitution studies further indicated that when kinase FA was reconstituted in acidic phospholipids, such as phosphatidylinositol and phosphatidylserine, the enzyme activity was inhibited in a dose-dependent manner, suggesting that kinase FA interacts with acidic phospholipids which inhibit its activity. Furthermore, when myelin was incubated with exogenous phospholipase C, the inactive/trypsin-resistant FA could be converted to the active/trypsin-labile FA in a time- and dose-dependent manner. Taken together, it is concluded that membrane phospholipids play an important role in modulating the activity of kinase FA in the brain myelin. It is suggested that phospholipase C may mediate the activation-sequestration of inactive/trypsin-resistant kinase FA in the brain myelin through the phospholipase C-catalyzed degradation of acidic membrane phospholipids. The activation-sequestration of protein kinase FA may represent one mode of control modulating the activity of kinase FA in the central nervous system myelin.
Yang
S D
SD
Institute of Life Science, National Tsing Hua University, Hsinchu, Taiwan, ROC.
Yu
J S
JS
Hua
C W
CW
D000818:Animals; D001921:Brain / Q000201:enzymology*; D002462:Cell Membrane / Q000201:enzymology; D004789:Enzyme Activation; D038362:Glycogen Synthase Kinase 3; D007527:Isoenzymes / Q000032:analysis; D008563:Membrane Lipids / Q000378:metabolism*; D009186:Myelin Sheath / Q000201:enzymology* / Q000648:ultrastructure; D010743:Phospholipids / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases; D011494:Protein Kinases / Q000032:analysis / Q000378:metabolism*; D013552:Swine; D014357:Trypsin
D007527:Isoenzymes; D008563:Membrane Lipids; D010743:Phospholipids; D011494:Protein Kinases; D038362:Glycogen Synthase Kinase 3; D010749:Phosphoprotein Phosphatases; D014357:Trypsin