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Oncogene. 2007 Oct 4;26(45):6536-45. Epub 2007 Apr 30.

Thirty-eight-negative kinase 1 (TNK1) facilitates TNFalpha-induced apoptosis by blocking NF-kappaB activation.

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  • 1Department of Internal Medicine I, University of Ulm, and Children's Hospital, Ulm, Germany.

Abstract

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 alpha (TNFalpha)-induced apoptosis by selectively inhibiting TNFalpha-induced activation of nuclear factor-kappaB (NF-kappaB). TNK1 has no effect on NF-kappaB DNA binding or the composition of the NF-kappaB complex; however, the kinase markedly prevents TNFalpha-induced NF-kappaB transactivation. TNK1 therefore acts as a novel molecular switch that can determine the properties of TNFalpha signaling and therefore cell death.

[PubMed - indexed for MEDLINE]
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