Abstract

Previously we reported that the activity of protein kinase FA/glycogen synthase kinase-3alpha (kinase FA/GSK-3alpha) can be detected in several brain membrane fractions. In this report, we examined whether kinase FA/GSK-3alpha can directly interact with membrane phospholipids by using anti-kinase FA/GSK-3alpha antibody as a more specific studying tool. It was found that kinase FA/GSK-3alpha can associate with NaOH-extracted brain membranes and selectively interact with several kinds of reconstituted phospholipid vesicles including phosphatidic acid (PA), phosphatidyl ethanolamine (PE), phosphatidyl inositol (PI), and phosphatidyl serine (PS) vesicles. Increasing ionic strength in the reaction could disrupt the interaction between kinase FA/GSK-3alpha and PA, PI, or PE vesicles but had no effect on the interaction between kinase FA/GSK-3alpha and PS vesicles, indicating that both ionic and non-ionic interactions are involved in this process, respectively. Moreover, both kinase activity and protease sensitivity of kinase FA/GSK-3alpha can be affected profoundly by these phospholipid vesicles and different forms of the kinase can be produced when it binds to distinct types of phospholipid vesicles. Taken together, the results demonstrate a direct interaction of kinase FA/GSK-3alpha with membrane phospholipids and suggest that membrane phospholipids may be directly involved in regulating kinase FA/GSK-3alpha activity.