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Kinase I (kinase + i)

Distribution by Scientific Domains
Life Sciences50%

Kinds of Kinase I

  • casein kinase i
    		•

    Selected Abstracts

    Casein Kinase I: From Obscurity to Center Stage

    IUBMB LIFE, Issue 2 2001
    Erica Vielhaber
    Abstract The casein kinase I (CKI) family of protein kinases is a group of highly related, ubiquitously expressed serine/threonine kinases found in all eukaryotic organisms from protozoa to man. Recent advances in diverse fields, including developmental biology and chronobiology, have elucidated roles for CKI in regulating critical processes such as Wnt signaling, circadian rhythm, nuclear import, and Alzheimer's disease progression. [source]

    The hinge region operates as a stability switch in cGMP-dependent protein kinase I,

    FEBS JOURNAL, Issue 9 2007
    Arjen Scholten
    The molecular mechanism of cGMP-dependent protein kinase activation by its allosteric regulator cyclic-3,,5,-guanosine monophosphate (cGMP) has been intensely studied. However, the structural as well as thermodynamic changes upon binding of cGMP to type I cGMP-dependent protein kinase are not fully understood. Here we report a cGMP-induced shift of Gibbs free enthalpy (,,GD) of 2.5 kJ·mol,1 as determined from changes in tryptophan fluorescence using urea-induced unfolding for bovine PKG I,. However, this apparent increase in overall stability specifically excluded the N-terminal region of the kinase. Analyses of tryptic cleavage patterns using liquid chromatography-coupled ESI-TOF mass spectrometry and SDS/PAGE revealed that cGMP binding destabilizes the N-terminus at the hinge region, centered around residue 77, while the C-terminus was protected from degradation. Furthermore, two recombinantly expressed mutants: the deletion fragment ,1-77 and the trypsin resistant mutant Arg77Leu (R77L) revealed that the labile nature of the N-terminus is primarily associated with the hinge region. The R77L mutation not only stabilized the N-terminus but extended a stabilizing effect on the remaining domains of the enzyme as well. These findings support the concept that the hinge region of PKG acts as a stability switch. [source]

    Wnt5a modulates glycogen synthase kinase 3 to induce phosphorylation of receptor tyrosine kinase Ror2

    GENES TO CELLS, Issue 11 2007
    Hiroyuki Yamamoto
    The receptor tyrosine kinase Ror2 plays important roles in mediating non-canonical Wnt5a signaling by activating the Wnt,JNK pathway and inhibiting the ,-catenin,TCF pathway. It has been shown that Ror2 is phosphorylated and activated by casein kinase I, when both molecules are over-expressed in cultured cells. However, it remains unknown whether or not Ror2 is phosphorylated upon Wnt5a stimulation. Here we show that Ror2 is phosphorylated on serine/threonine residues upon stimulation of cultured cells, expressing Ror2 endogenously, with Wnt5a, but not Wnt3a. It was found that treatment of cells with glycogen synthase kinase-3 (GSK-3) inhibitors (LiCl and SB216763) or small interfering RNAs (siRNAs) for GSK-3 (mainly GSK-3,) can inhibit Wnt5a-induced phosphorylation of Ror2. Immunoprecipitated Ror2 can also be phosphorylated by purified GSK-3, or GSK-3,in vitro, and ectopic co-expression of Ror2 and GSK-3 (mainly GSK-3,) in cultured cells results in Ror2 phosphorylation, irrespective of Wnt5a, that is sensitive to SB216763. These results indicate that GSK-3 is involved in Wnt5a-induced phosphorylation of Ror2. Moreover, it was found that Wnt5a-induced cell migration can be inhibited by SB216763 or by siRNA-mediated suppression of GSK-3, (and GSK-3,) expression, further emphasizing the role(s) of GSK-3 in Wnt5a-induced signaling. [source]

    Disease-associated casein kinase I , mutation may promote adenomatous polyps formation via a Wnt/,-catenin independent mechanism

    INTERNATIONAL JOURNAL OF CANCER, Issue 5 2007
    I-Chun Tsai
    Abstract The Wnt signaling pathway is critical for embryonic development and is dysregulated in multiple cancers. Two closely related isoforms of casein kinase I (CKI, and ,) are positive regulators of this pathway. We speculated that mutations in the autoinhibitory domain of CKI,/, might upregulate CKI,/, activity and hence Wnt signaling and increase the risk of adenomatous polyps and colon cancer. Exons encoding the CKI, and CKI, regulatory domains were sequenced from DNA obtained from individuals with adenomatous polyps and a family history of colon cancer unaffected by familial adenomatous polyposis or hereditary nonpolyposis colorectal cancer (HNPCC). A CKI, missense mutation, changing a highly conserved residue, Arg324, to His (R324H), was found in an individual with large and multiple polyps diagnosed at a relatively young age. Two findings indicate that this mutation is biologically active. First, ectopic ventral expression of CKI,(R324H) in Xenopus embryos results in secondary axis formation with an additional distinctive phenotype (altered morphological movements) similar to that seen with unregulated CKI,. Second, CKI,(R324H) is more potent than wildtype CKI, in transformation of RKO colon cancer cells. Although the R324H mutation does not significantly change CKI, kinase activity in an in vitro kinase assay or Wnt/,-catenin signal transduction as assessed by a ,-catenin reporter assay, it alters morphogenetic movements via a ,-catenin-independent mechanism in early Xenopus development. This novel human CKI, mutation may alter the physiological role and enhance the transforming ability of CKI, through a Wnt/,-catenin independent mechanism and thereby influence colonic adenoma development. © 2006 Wiley-Liss, Inc. [source]

    Interaction of 14-3-3 with Bid during seizure-induced neuronal death

    JOURNAL OF NEUROCHEMISTRY, Issue 2 2003
    Sachiko Shinoda
    Abstract Seizure-induced neuronal death may involve coordinated intracellular trafficking and protein,protein interactions of members of the Bcl-2 family. The 14-3-3 proteins are known to sequester certain pro-apoptotic members of this family. BH3-interacting domain death agonist (Bid) may contribute to seizure-induced neuronal death, although regulation by 14-3-3 has not been reported. In this study we examined whether 14-3-3 proteins interact with Bid during seizure-induced neuronal death. Brief seizures were evoked in rats by intraamygdala microinjection of kainic acid to elicit unilateral hippocampal CA3 neuronal death. Coimmunoprecipitation analysis demonstrated that although Bcl-2-associated death promoter (Bad) constitutively bound 14-3-3, there was no interaction between Bid and 14-3-3 in control brain. Seizures triggered Bid cleavage and a commensurate increase in binding of Bid to 14-3-3 within injured hippocampus. Casein kinases I and II, which can inactivate Bid by phosphoserine/threonine modification, did not coimmunoprecipitate with Bid. The largely uninjured contralateral hippocampus did not exhibit Bid cleavage or binding of 14-3-3 to Bid. In vitro experiments confirmed that 14-3-3, is capable of binding truncated Bid, likely in the absence of phosphoserine/threonine modification. These data suggest 14-3-3 proteins may target active as well as inactive conformations of pro-apoptotic Bcl-2 death agonists, highlighting novel targets for intervention in seizure-induced neuronal death. [source]