Two genes in Saccharomyces cerevisiae encode a membrane-bound form of casein kinase-1.

Wang, P C; Vančura, Aleš; Mitcheson, T G; Kuret, Jeff

doi:10.1091/mbc.3.3.275

Cited by 97 publications

(81 citation statements)

References 59 publications

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“…First, the major phosphorylation sites within Pdr5p were identified as serine residues. Second, Pdr5p phosphorylation was prevented either by 0.1 mM Zn 2ϩ , which inhibits casein kinase I activity (44), or by mutations in the YCK1 and YCK2 genes, which encode plasma membrane-bound isoforms of casein kinase I (52,53). One of the phosphorylatable residues, Ser 420 , was found within the sequence Thr 419 -Ser-Val-Thr-Ser-Pro 424 , which conforms with the casein kinase I phosphorylation site motif, Xaa-Ser(P)-Xaa-Xaa-Ser*-Xaa, in which the asterisk indicates the phosphorylated residue and (P) denotes a phosphorylated residue that acts as a substrate specificity determinant (55).…”

Section: Discussionmentioning

confidence: 99%

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Casein Kinase I-dependent Phosphorylation and Stability of the Yeast Multidrug Transporter Pdr5p

Decottignies¹,

Owsianik²,

Ghislain

1999

Journal of Biological Chemistry

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The pleiotropic drug resistance protein, Pdr5p, is an ATP-binding cassette transporter of the plasma membrane of Saccharomyces cerevisiae. Overexpression of Pdr5p results in increased cell resistance to a variety of cytotoxic compounds, a phenotype reminiscent of the multiple drug resistance seen in tumor cells. Pdr5p and two other yeast ATP-binding cassette transporters, Snq2p and Yor1p, were found to be phosphorylated on serine residues in vitro. Mutations in the plasma membrane-bound casein kinase I isoforms, Yck1p and Yck2p, abolished Pdr5p phosphorylation and modified the multiple drug resistance profile. We showed Pdr5p to be ubiquitylated when overexpressed. However, instability of Pdr5p was only seen in Yck1p-and Yck2p-deficient strains, in which it was degraded in the vacuole via a Pep4p-dependent mechanism. Our results suggest that casein kinase I activity is required for membrane trafficking of Pdr5p to the cell surface. In the absence of functional Yck1p and Yck2p, Pdr5p is transported to the vacuole for degradation.

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Section: Discussionmentioning

confidence: 99%

“…Phosphorylation of Pdr5p Is Impaired in Casein Kinase I-deficient Strains-Plasma membrane-associated casein kinase I activity is encoded by the YCK1 and YCK2 genes (52,53). The absence of either gene has no discernible effect on cell growth, but the loss of both genes is lethal (52).…”

Section: In Vitro Phosphorylation Of Yeast Plasma Membrane Abcmentioning

confidence: 99%

Casein Kinase I-dependent Phosphorylation and Stability of the Yeast Multidrug Transporter Pdr5p

Decottignies¹,

Owsianik²,

Ghislain

1999

Journal of Biological Chemistry

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“…The CK1 family of enzymes phosphorylates a variety of physiological substrates including transcription factor CREM (31), glycogen synthase (32), p53 (33), and the SV40 T antigen (34). Individual CK1 isoforms in lower eukaryotes are found in the cytoplasm as well as in the nuclei and play essential roles in the regulation of cellular morphogenesis and DNA repair (35)(36)(37). Self-phosphorylation of malarial cytoplasmic extracts revealed a number of phosphoproteins (Refs.…”

Section: Discussionmentioning

confidence: 99%

Identification, Cloning, and Mutational Analysis of the Casein Kinase 1 cDNA of the Malaria Parasite, Plasmodium falciparum

Barik

Taylor

Chakrabarti

1997

Journal of Biological Chemistry

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The cDNA for casein kinase 1 (CK1) of Plasmodium falciparum was cloned, sequenced, and expressed in bacteria. The single major open reading frame of the 1.2-kilobase pair cDNA coded for a 324-amino acid polypeptide of ϳ37 kDa, the predicted sequence of which showed strong identity with known CK1 isoforms. The purified recombinant enzyme exhibited properties characteristic of CK1, such as inhibition by CK1-7, the ability to phosphorylate a highly specific peptide substrate, and a strong preference for ATP over GTP. A casein kinase activity, partially purified from soluble extracts of P. falciparum by affinity chromatography through CK1-7 columns displayed identical properties. The activity showed a stage-specific expression in the parasite, in the order trophozoite > ring > > schizont. Northern analysis indicated the existence of two major CK1 mRNAs, 2.4 and 3.2 kilobase pairs long, the levels of which were in the order ring > schizont > trophozoite. Mutagenesis of recombinant CK1 defined important amino acid residues and their potential role in the conformation of the enzyme. The malarial CK1 appeared to be the one of the smallest and perhaps the most primitive CK1 enzymes known, containing little sequence information beyond the minimal catalytic domain.The parasitic protozoan, Plasmodium falciparum, is the causative agent of malaria throughout the world and is responsible for an annual death toll of nearly 3 million, the majority of which are children and pregnant mothers (1). However, tools available to control malaria are inadequate, and drug-resistant strains are widespread; moreover, the immediate prospect of a useful vaccine is uncertain. Thus, there is an urgent need to obtain fundamental knowledge about the various cellular processes of P. falciparum at the molecular level, so that susceptible targets can be identified. With this long-term goal in mind, we have initiated studies of the signal transduction system in P. falciparum. Since reversible protein phosphorylation and dephosphorylation constitute a major mechanism of signal transduction (2), one of our immediate goals has been to characterize the various protein kinases in P. falciparum. In this paper, we report the characterization, expression, stagespecific regulation, and mutational analysis of P. falciparum casein kinase 1 (PfCK1). 1 Casein kinase-1 and -2 (CK1 and CK2) are multipotential Ser/Thr protein kinases, originally purified from rabbit reticulocyte lysates using casein as substrate (reviewed in Refs. 3 and 4). In the subsequent years, both enzymes were shown to phosphorylate, and thus regulate, a wide variety of cellular proteins. The sequence alignment of CK1 genes of various organisms and deletion analysis of recombinant yeast CK1 have recently resulted in the delineation of the following domains in the prototype 45-kDa yeast enzyme (summarized in Refs. 5 and 6): an N-terminal catalytic domain of about 300 amino acids followed by a 12-residue stretch conserved among some forms but not in others; a hydrophilic 85-residue segment predi...

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“…Proteins were stained with Coomassie Brilliant Blue R (Murthy et al, 1994). Automated Edman degradation was performed on an Applied Biosystems Procise Sequencer essentially as described previously (Wang et al, 1992). Initial yields were calculated from regression analysis of residue yields per cycle, and ranged at 8-1,800 pmol for all peptides.…”

Section: Methodsmentioning

confidence: 99%

Cross‐Linking Sites of the Human Tau Protein, Probed by Reactions with Human Transglutaminase

Murthy

Wilson

Lukas

et al. 1998

Journal of Neurochemistry

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A portion of the neurofibrillary tangles of Alzheimer's disease has the characteristics of cross-linked protein. Because the principal component of these lesions is the microtubule-associated protein tau, and because a major source of cross-linking activity within neurons is supplied by tissue transglutaminase (TGase), it has been postulated that isopeptide bond formation is a major posttranslational modification leading to the formation of insoluble neurofibrillary tangles. Here we have mapped the sites on two isoforms of human tau protein (r23 and 40) capable of participating in human TGase-mediated isopeptide bond formation. Using dansyl-labeled fluorescent probes, it was shown that eight Gin residues can function as amine acceptor residues, with two major sites being Gin 351 and Gin424. In addition, 10 Lys residues were identified as amine donors, most of which are clustered adjacent to the microtubule-binding repeats of tau in regions known to be solvent accessible in filamentous tau. The distribution of amine donors correlated closely with that of Arg residues, suggesting a link between neighboring positive charge and the TGase selectivity for donor sites in the protein substrate. Apart from revealing the sites that can be cross-linked during the TGase-catalyzed assembly of tau filaments, the results suggest a topography for the tau monomers so assembled. Key Words: Alzheimer's disease-Neurofibrillary tangles-Paired helical filament-Tau protein -Transglutaminase.

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Two genes in Saccharomyces cerevisiae encode a membrane-bound form of casein kinase-1.

Cited by 97 publications

References 59 publications

Casein Kinase I-dependent Phosphorylation and Stability of the Yeast Multidrug Transporter Pdr5p

Casein Kinase I-dependent Phosphorylation and Stability of the Yeast Multidrug Transporter Pdr5p

Identification, Cloning, and Mutational Analysis of the Casein Kinase 1 cDNA of the Malaria Parasite, Plasmodium falciparum

Cross‐Linking Sites of the Human Tau Protein, Probed by Reactions with Human Transglutaminase

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