Synergistic activation of NF-kappa B by functional cooperation between Vavand PKC theta in T lymphocytes

Here we identified PKC theta as an activator of transcription factor NF-kap pa B in T cells. PK theta-induced NF-kappa B activation was synergistically augmented by Vav, Several experimental approaches revealed that PKC theta is located downstream from Vav in the control of the pathway leading to syn ergistic NF-kappa B activation. In addition to the synergistic activation c ascade, Vav also triggered NF-kappa B activity on a separate route. CD3/CD2 8-induced activation of NF-kappa B was inhibited by dominant negative forms of Vav or PKC theta, revealing their essential role in this activation pat hway. The Vav/PKC theta-mediated signals preferentially activated I kappa B kinase P. Vav and PRC theta were found to be constitutively associated in unstimulated T cells. Only the ligation of the costimulatory CD28 receptor, but not of the T cell receptor, resulted in the transient dissociation of the Vav-PKC theta complex. In contrast, T cell receptor/CD28 costimulation resulted in faster dissociation and slower reassociation kinetics.