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(Journal of Leukocyte Biology. 2001;70:649-658.)
© 2001 by Society for Leukocyte Biology

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

Erick García-García, Gabriela Sánchez-Mejorada and Carlos Rosales

Immunology Department, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City

Correspondence: Dr. Carlos Rosales, Department of Immunology, Instituto de Investigaciones Biomédicas—UNAM, Apto. Postal 70228, Cd. Universitaria, México D.F.-04510, Mexico. E-mail: carosal{at}servidor.unam.mx

The molecular events that transduce signals from Fc receptors to the various cellular responses are still poorly defined. We have investigated the role of phosphatidylinositol 3-kinase (PI 3-K) and extracellular signal-regulated kinase (ERK) in gene activation and phagocytosis in monocytes. In the THP-1 monocytic cell line, cross-linking of Fc receptors by immune complexes results in activation of the transcription factor NF-{kappa}B, via activation of ERK. Activation of both ERK and NF-{kappa}B was blocked by wortmannin and LY294002, specific inhibitors of PI 3-K. Wortmannin also inhibited the Fc receptor-mediated increase in the cytosolic calcium concentration, but it did not block immunoglobulin G (IgG)-mediated phagocytosis. In addition, the ERK inhibitor PD98059 did not block phagocytosis of IgG-coated erythrocytes. Both the increase in the cytosolic calcium concentration and phagocytosis depend on an active actin cytoskeleton, as indicated by the total lack of both responses after treatment with cytochalasin B. In contrast, cytochalasin B did not affect Fc receptor-mediated activation of NF-{kappa}B. These results identify PI 3-K and ERK as important signaling molecules in the Fc receptor signal transduction pathway of monocytes, which leads to the nucleus for gene activation. These results also suggest that, in contrast to other cell types, unstimulated monocytes do not require PI 3-K and ERK for phagocytosis.

Key Words: monocytes • signal transduction • Fc receptors




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