Phosphatidylinositol-4,5-bisphosphate mediates the interaction of syndecan-4 with protein kinase C.

Recent studies have demonstrated that the cytoplasmic tail of syndecan-4, a widely expressed transmembrane proteoglycan, can activate protein kinase Cα in vitro, in combination with phosphatidylinositol-4,5-bisphosphate (PI-4,5-P2). Syndecan-4 is involved in growth factor binding as well as in adhesion to extracellular matrix proteins, while PI-4,5-P2 synthesis is modulated by growth factor and adhesion-generated signaling. The cooperative activation of PKCα by the proteoglycan and the phosphatidylinositol may constitute, therefore, an essential part of the cell's response to these extracellular signals. To characterize the activation mechanism of PKCα, we addressed here the nature of the interplay between syndecan-4, PI-4,5-P2, and PKCα by measuring their mutual binding affinities and the specificity of their interactions. We found that the cytoplasmic tail of syndecan-4 is unlikely to bind directly to PKCα, and that this interaction critically depends on PI-4,5-P2. The PI-4,5-P2 specificity of the activ...