Abstract
Syndecans are proteoglycans that act as signaling molecules. Previously, we showed that syndecan‐2 (SYND2) is involved in the control of osteoblastic (OB) cell apoptosis. Here, we show a novel functional interaction between SYND2 and protein kinase C δ (PKCδ). Overexpression of SYND2 in MG63 OB cells resulted in increased PKCδ protein level without change in PKCδ mRNA production. In SYND2‐transfected cells, the increase in PKCδ was restricted to the cytosolic compartment, threonine 505‐PKCδ was underphosphorylated and immunoprecipitated PKCδ showed decreased capacity to phosphorylate histone, indicating that SYND2 decreased PKCδ activity. Inhibition of PKCδ by Rottlerin or a dead‐kinase dominant negative (DN) construct activated effector caspases and increased the number of apoptotic cells. In addition, rescue of kinase activity with a construct coding, the PKCδ catalytic domain (CAT) reduced SYND2‐induced apoptosis. This indicates that PKCδ acts as a pro‐survival kinase and that SYND2 inhibits the anti‐apoptotic action of PKCδ in OB cells. We also showed that overexpression of PKCδ wild type (WT) induced osteoblast apoptosis. Moreover, inhibition of PKCδ by siRNA resulted in increased apoptosis in control cells but reduced apoptosis in SYND2‐overexpressing osteoblasts, indicating that SYND2 requires PKCδ accumulation to induce apoptosis. These results show that SYND2 modulates PKCδ actions by inhibition of the canonical allosterical activation pathway that plays an anti‐apoptotic role in OB cells, and promotion of a pro‐apoptotic role that may depend on PKCδ protein level and that participates to the induction of cell death by SYND2. This establishes a functional interaction between SYND2 and PKCδ in osteoblasts. J. Cell. Biochem. 98: 838–850, 2006. © 2006 Wiley‐Liss, Inc.