Phosphatidylinositol 3-kinase and ERK are required for NF-kappa B activation but not for phagocytosis

The molecular events that transduce signals from Fe receptors to the variou s cellular responses are still poorly defined. We have investigated the rol e of phosphatidylinositol 3-kinase (PI 3-K) and extracellular signal-regula ted kinase (ERK) in gene activation and phagocytosis in monocytes. In the T HP-1 monocytic cell line, cross-linking of Fe receptors by immune complexes results in activation of the transcription factor NF-kappaB, via activatio n of ERK. Activation of both ERK and NF-kappaB was blocked by wortmannin an d LY294002, specific inhibitors of PI 3-K. Wortmannin also inhibited the Fe receptor-mediated increase in the cytosolic calcium concentration, but it did not block immunoglobulin G (IgG)-mediated phagocytosis. In addition, th e ERK inhibitor PD98059 did not block phagocytosis of IgG-coated erythrocyt es. Both the increase in the cytosolic calcium concentration and phagocytos is depend on an active actin cytoskeleton, as indicated by the total lack o f both responses after treatment with cytochalasin B. In contrast, cytochal asin B did not affect Fe receptor-mediated activation of NF-kappaB. These r esults identify PI 3-K and ERK as important signaling molecules in the Fe r eceptor signal transduction pathway of monocytes, which leads to the nucleu s for gene activation. These results also suggest that, Mi contrast to othe r cell types, unstimulated monocytes do not require PI 3-K and ERK for phag ocytosis.