Hematopoietic progenitor kinase-1 (HPK1) stress response signaling pathwayactivates I kappa B kinases (IKK-alpha/beta) and IKK-beta is a developmentally regulated protein kinase

Nuclear factor kappa-B (NF-kappa B) is a pleiotropic transcription factor t hat plays a central role in the immune and inflammatory responses, and is a lso involved in controlling viral transcription and apoptosis, A critical c ontrol in the activation of NF-kappa B is the phosphorylation of its inhibi tory factor I kappa Bs by I kappa B kinases (IKK-alpha and -beta). Here, we present experiments addressing the regulation and global expression of mur ine IKK-beta, and localize the IKK-beta gene to mouse chromosome 8A3-A4. IK K-beta was expressed primarily in the liver, kidney and spleen, and at lowe r levels in the other adult tissues. While IKK-beta was expressed ubiquitou sly throughout the mouse embryo at 9.5 days, its expression began to be loc alized 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 t o specific tissues of the embryo, suggesting that IKK-beta is a development ally regulated protein kinase, Interestingly, IKK-beta phosphorylated I kap pa B constitutively, whereas IKK-alpha was not active in the absence of cel l stimulation, Moreover, both IKK-alpha and -beta were activated by hematop oietic progenitor kinase-1 (HPK1) and MAPK/ERK kinase kinase-1 (MEKK1) spec ifically, suggesting that I kappa B/NF-kappa B is regulated through the HPK 1-MEKK1 stress response signaling pathway.