IL-2 SIGNALING CONTROLS ACTIN ORGANIZATION THROUGH RHO-LIKE PROTEIN FAMILY, PHOSPHATIDYLINOSITOL 3-KINASE, AND PROTEIN-KINASE C-ZETA

IL-2 and IL-4 induce proliferation of TS1 alpha beta cells. Activation of the zeta isoform of protein kinase C is an important step in IL-2- , but not IL-4-mediated proliferation. In addition, protein kinase C-z eta is implicated in IL-2-mediated actin organization. Given the estab lished involvement of the Rho family of small guanine nucleotide-bindi ng proteins in organization of actin structures, we analyze the possib le relationships between Rho and protein kinase C-zeta. Using the Rho- like protein family-specific toxin B from Clostridium difficile, we re port in this work that IL-2, but not IL-4, induces a Rho-dependent act ivation of protein kinase C-zeta. This signaling event is mediated by the activation of phosphatidylinositol S-kinase. In contrast, IL-4 ind uces a Rho-independent, phosphatidylinositol 3-kinase-mediated activat ion of protein kinase C-zeta, but this pathway has no implications in cytoskeleton organization.