K562 cell proliferation is modulated by PLC beta 1 through a PKC alpha-mediated pathway

Phospholipase C beta 1 (PLC beta 1) is known to play an important role in cell proliferation. previous studies reported an involvement of PLC beta 1 in G(0)-G(1)/S transition and G(2)/M progression in Friend murine erythroleukemia cells (FELC). However, little has been found about its role in human models. Here, we used K562 cell line as human homologous of FELC in order to investigate the possible key regulatory role of PLC beta 1 during cell proliferation of this human cell line. our studies on the efects of the overexpression of both these isoforms showed a specific and positive connection between cyclin D3 and PLC beta 1 in K562 cells, which led to a prolonged S phase of the cell cycle and a delay in cell proliferation. In order to shed light on this mechanism, we decided to study the possible involvement of protein kinases C (PKC), known to be direct targets of PLC signaling and important regulators of cell proliferation. our data showed a peculiar decrease of PKC alpha levels in cells overexpressing PLC beta 1. Moreover, when we silenced PKC alpha, by RNAi technique, in order to mimic the efects of PLC beta 1, we caused the same upregulation of cyclin D3 levels and the same decrease of cell proliferation found in PLC beta 1-overexpressing cells. the key features emerging from our studies in K562 cells is that PLC beta 1 targets cyclin D3, likely through a PKC alpha-mediated-pathway, and that, as a downstream effect of its activity, K562 cells undergo an accumulation in the S phase of the cell cycle.