title: Hematopoietic progenitor kinase-1 (HPK1) stress response signaling pathway activates IkappaB kinases (IKK-alpha/beta) and IKK-beta is a developmentally regulated protein kinase.
abstract: 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.
authors.affiliation: Department of Cell Biology, Amgen, Inc., Thousand Oaks, California, CA 91320, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Hu
authors.forename: Y p
authors.initials: Yp
authors.lastname: Wang
authors.forename: W R
authors.initials: WR
authors.lastname: Qiu
authors.forename: A
authors.initials: A
authors.lastname: Mikhail
authors.forename: C F
authors.initials: CF
authors.lastname: Meyer
authors.forename: T H
authors.initials: TH
authors.lastname: Tan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D018076:DNA, Complementary / Q000235:genetics; D004789:Enzyme Activation; D004790:Enzyme Induction; D020224:Expressed Sequence Tags; D005326:Fetal Proteins / Q000096:biosynthesis / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D005796:Genes; D006801:Humans; D051550:I-kappa B Kinase; D020672:I-kappa B Proteins / Q000378:metabolism*; D017404:In Situ Hybridization, Fluorescence; D048728:MAP Kinase Kinase Kinase 1; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice / Q000235:genetics*; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013312:Stress, Physiological / Q000201:enzymology / Q000235:genetics
chemical_list: D018076:DNA, Complementary; D005326:Fetal Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; C102102:hematopoietic progenitor kinase 1; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human; C496562:Ikbkb protein, mouse; C496566:Ikbke protein, mouse; D048728:MAP Kinase Kinase Kinase 1; D020930:MAP Kinase Kinase Kinases; C482576:MAP3K1 protein, human; C482578:Map3k1 protein, mouse