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

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