Hematopoietic progenitor kinase-1 (HPK1) stress response signaling pathway activates IκB kinases (IKK-α/β) and IKK-β is a developmentally regulated protein kinase

Mickey C.T. Hu, You Ping Wang, Wan R. Qiu, Adel Mikhail, Christian F. Meyer, Tse Hua Tan

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Nuclear factor kappa-B (NF-κB) is a pleiotropic transcription factor that plays a central role in the immune and inflammatory responses, and is also involved in controlling viral transcription and apoptosis. A critical control in the activation of NF-κB is the phosphorylation of its inhibitory factor Iκ-Bs by IκB kinases (IKK-α and -β). Here, we present experiments addressing the regulation and global expression of murine IKK-β, and localize the IKK-β gene to mouse chromosome 8A3-A4, IKK-β was expressed primarily in the liver, kidney and spleen, and at lower levels in the other adult tissues. While IKK-β was expressed ubiquitously throughout the mouse embryo at 9.5 days, its expression began to be localized to the brain, neural ganglia, neural tube, and liver in the 12.5-day's embryo. At 15.5 days, the expression of IKK-β was further restricted to specific tissues of the embryo, suggesting that IKK-β is a developmentally regulated protein kinase. Interestingly, IKK-β phosphorylated IκB constitutively, whereas IKK-α was not active in the absence of cell stimulation. Moreover, both IKK-α and -β were activated by hematopoietic progenitor kinase-1 (HPK1) and MAPK/ERK kinase kinase-1 (MEKK1) specifically, suggesting that IκB/NF-κB is regulated through the HPK1-MEKK1 stress response signaling pathway.

Original languageEnglish (US)
Pages (from-to)5514-5524
Number of pages11
JournalOncogene
Volume18
Issue number40
DOIs
StatePublished - Sep 30 1999
Externally publishedYes

Keywords

  • HPK1
  • IκB
  • MEKK1
  • NF-κB
  • Protein kinase
  • Signal transduction

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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