Protein kinase C alpha can undergo membrane localization via an alternative phosphatidylinositol 4,5-bisphosphate-dependent pathway

摘要

Protein kinase C alpha (PKC alpha) activation is known to be dependent on the metabolic product of phosphatidylinositol 4,5-bisphosphate (PIP,) by phospholipase C (PLC). Here we report that fibroblasts may have an additional PIP2-dependent mechanism for membrane localization of PKC alpha. We observed PKC alpha membrane localization in both wild type and PLC gamma 1-/- mouse embryonic fibroblasts. Treatment of cells with a specific PLC inhibitor U73122 resulted in increased PIP2 levels and enhanced membrane localization of PKC alpha. PKC alpha levels in the membrane fraction decreased following incubation with PLC gamma, but increased following treatment with U73122 or addition of exogenous PIP2 in vitro. In addition, PKC alpha interacted with PIP2-conjugate bead and mixed micelles containing PIP2. Finally, we found that PIP, is involved in syndecan-4-mediated membrane localization of PKC alpha. Taken together, these data suggest that PIP, might contribute to directly regulating the membrane localization of PKC alpha.. (c) 2006 Elsevier Inc. All rights reserved.