Thirty-eight-negative kinase 1 (TNK1) facilitates TNFα-induced apoptosis by blocking NF-κB activation

Thirty-eight-negative kinase 1 (TNK1) is a member of the ACK-family of nonreceptor tyrosine kinases and was originally cloned from CD34+/Lin-/CD38-hematopoietic stem/progenitor cells. The signaling pathways induced by TNK1 are largely unknown. Here, we report that expression and consequent activation of TNK1 enables tumor necrosis factor a (TNF alpha)-induced apoptosis by selectively inhibiting TNF alpha-induced activation of nuclear factor-kappa B (NF-kappa B). TNK1 has no effect on NF-kappa B DNA binding or the composition of the NF-kappa B complex; however, the kinase markedly prevents TNFa-induced NF-kappa B transactivation. TNK1 therefore acts as a novel molecular switch that can determine the properties of TNFa signaling and therefore cell death.