Hematopoietic progenitor kinase-1 (HPK1) stress response signaling pathway activates IkappaB kinases (IKK-alpha/beta) and IKK-beta is a developmentally regulated protein kinase.

Nuclear factor kappa-B (NF-kappaB) 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-kappaB is the phosphorylation of its inhibitory factor IkappaBs by IkappaB 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, neural 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 IkappaB 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 IkappaB/NF-kappaB is regulated through the HPK1-MEKK1 stress response signaling pathway.