Protein kinase C modulates the catalytic activity of topoisomerase II by enhancing the rate of ATP hydrolysis: evidence for a common mechanism of regulation by phosphorylation

Biochemistry ◽  
1993 ◽  
Vol 32 (8) ◽  
pp. 2090-2097 ◽  
Author(s):  
Anita H. Corbett ◽  
Amy W. Fernald ◽  
Neil Osheroff
Keyword(s):  
Protein Kinase C ◽  
Catalytic Activity ◽  
Protein Kinase ◽  
Topoisomerase Ii ◽  
Atp Hydrolysis ◽  
Common Mechanism ◽  
Kinase C

scholarly journals Protein kinase C in rod outer segments: effects of phosphorylation of the phosphodiesterase inhibitory subunit

1996 ◽  
Vol 317 (1) ◽  
pp. 291-295 ◽  
Author(s):  
Igor P. UDOVICHENKO ◽  
Jess CUNNICK ◽  
Karen GONZALEZ ◽  
Alexander YAKHNIN ◽  
Dolores J. TAKEMOTO
Keyword(s):  
Protein Kinase C ◽  
Catalytic Activity ◽  
Protein Kinase ◽  
Direct Interaction ◽  
Inhibitory Effect ◽  
Rod Outer Segments ◽  
Visual Transduction ◽  
Gtp Hydrolysis ◽  
Outer Segments ◽  
Kinase C

The inhibitory subunit (PDEγ) of the cGMP phosphodiesterase (PDEαβγ2) in rod outer segments (ROS) realizes its regulatory role in phototransduction by inhibition of PDEαβ catalytic activity. The photoreceptor G-protein, transducin, serves as a transducer from the receptor (rhodopsin) to the effector (PDE) and eliminates the inhibitory effect of PDEγ by direct interaction with PDEγ. Our previous study [Udovichenko, Cunnick, Gonzalez and Takemoto (1994) J. Biol. Chem. 269, 9850–9856] has shown that PDEγ is a substrate for protein kinase C (PKC) from ROS and that phosphorylation by PKC increases the ability of PDEγ to inhibit PDEαβ catalytic activity. Here we report that transducin is less effective in activation of PDEαβ(γp)2 (a complex of PDEαβ with phosphorylated PDEγ, PDEγp) than PDEαβγ2. PDEγp also increases the rate constant of GTP hydrolysis of transducin (from 0.16 s-1 for non-phosphorylated PDEγ to 0.21 s-1 for PDEγp). These data suggest that phosphorylation of the inhibitory subunit of PDE by PKC may regulate the visual transduction cascade by decreasing the photoresponse.

scholarly journals Analysis of the water-soluble products of phosphatidylcholine breakdown by ion-exchange chromatography. Bombesin and TPA (12-O-tetradecanoylphorbol 13-acetate) stimulate choline generation in Swiss 3T3 cells by a common mechanism

1989 ◽  
Vol 263 (2) ◽  
pp. 581-587 ◽  
Author(s):  
S J Cook ◽  
M J O Wakelam
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Ion Exchange ◽  
Water Soluble ◽  
Common Mechanism ◽  
3T3 Cells ◽  
Kinase C ◽  
Choline Phosphate ◽  
Swiss 3T3 ◽  
Stimulation Of

A method for the rapid and quantitative separation of glycerophosphocholine, choline phosphate and choline upon ion-exchange columns is described. The method has been utilized to examine the stimulation of phosphatidylcholine breakdown in quiescent Swiss 3T3 cells in response to bombesin and 12-O-tetradecanoylphorbol 13-acetate (TPA). The stimulated generation of choline is shown to precede that of choline phosphate, with no effect upon glycerophosphocholine levels; but was attenuated in cells in which protein kinase C activity was down-regulated. The results thus suggest that stimulation of the cells with either bombesin or TPA activates phospholipase D-catalysed phosphatidylcholine breakdown by a common mechanism involving the activation of protein kinase C.

Antiproliferative actions of 7-substituted 1,3-dihydroxyacridones; possible involvement of DNA topoisomerase II and protein kinase C as biochemical targets

1994 ◽  
Vol 2 (12) ◽  
pp. 1403-1411 ◽  
Author(s):  
Kenneth F. Bastow ◽  
Masataka Itoigawa ◽  
Hiroshi Furukawa ◽  
Yoshiki Kashiwada ◽  
Ibrahim D. Bori ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Topoisomerase Ii ◽  
Dna Topoisomerase Ii ◽  
Dna Topoisomerase ◽  
Kinase C

Regulation of Jak2 tyrosine kinase by protein kinase C during macrophage differentiation of IL-3–dependent myeloid progenitor cells

Blood ◽  
2000 ◽  
Vol 95 (5) ◽  
pp. 1626-1632 ◽  
Author(s):  
Panu E. Kovanen ◽  
Ilkka Junttila ◽  
Kati Takaluoma ◽  
Pipsa Saharinen ◽  
Leena Valmu ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Catalytic Activity ◽  
Protein Kinase ◽  
Tyrosine Kinase ◽  
Progenitor Cells ◽  
Growth Arrest ◽  
Macrophage Differentiation ◽  
Myeloid Progenitor ◽  
Kinase C ◽  
Myeloid Progenitor Cells

Differentiation of macrophages from myeloid progenitor cells depends on a discrete balance between cell growth, survival, and differentiation signals. Interleukin-3 (IL-3) supports the growth and survival of myeloid progenitor cells through the activation of Jak2 tyrosine kinase, and macrophage differentiation has been shown to be regulated by protein kinase C (PKC). During terminal differentiation of macrophages, the cells lose their mitogenic response to IL-3 and undergo growth arrest, but the underlying signaling mechanisms have remained elusive. Here we show that in IL-3–dependent 32D myeloid progenitor cells, the differentiation-inducing PKC isoforms PKC- and PKC-δ specifically caused rapid inhibition of IL-3–induced tyrosine phosphorylation. The target for this inhibition was Jak2, and the activation of PKC by 12-O-tetradecanoyl-phorbol-13-acetate treatment also abrogated IL-3–induced tyrosine phosphorylation of Jak2 in Ba/F3 cells. The mechanism of this regulation was investigated in 32D and COS7 cells, and the inhibition of Jak2 required catalytic activity of PKC-δ and involved the phosphorylation of Jak2 on serine and threonine residues by the associated PKC-δ. Furthermore, PKC-δ inhibited the in vitro catalytic activity of Jak2, indicating that Jak2 was a direct target for PKC-δ. In 32D cells, the inhibition of Jak2 either by PKC-δ, tyrosine kinase inhibitor AG490, or IL-3 deprivation caused a similar growth arrest. Reversal of PKC-δ–mediated inhibition by the overexpression of Jak2 promoted apoptosis in differentiating 32D cells. These results demonstrate a PKC-mediated negative regulatory mechanism of cytokine signaling and Jak2, and they suggest that it serves to integrate growth-promoting and differentiation signals during macrophage differentiation.

scholarly journals Decreased Catalytic Activity and Expression of Protein Kinase C Isozymesin Teenage Suicide Victims

2004 ◽  
Vol 61 (7) ◽  
pp. 685 ◽  
Author(s):  
Ghanshyam N. Pandey ◽  
Yogesh Dwivedi ◽  
Hooriyah S. Rizavi ◽  
Xinguo Ren ◽  
Robert R. Conley
Keyword(s):  
Protein Kinase C ◽  
Catalytic Activity ◽  
Protein Kinase ◽  
Kinase C ◽  
Teenage Suicide

scholarly journals Yeast phenotype classifies mammalian protein kinase C cDNA mutants.

1993 ◽  
Vol 13 (8) ◽  
pp. 4728-4735 ◽  
Author(s):  
H Riedel ◽  
L Su ◽  
H Hansen
Keyword(s):  
Protein Kinase C ◽  
Catalytic Activity ◽  
Protein Kinase ◽  
Phorbol Ester ◽  
Colony Size ◽  
Receptor Protein ◽  
Amino Terminal ◽  
Kinase C ◽  
Carboxyl Terminal ◽  
Pkc Alpha

The phorbol ester receptor protein kinase C (PKC) gene family encodes essential mediators of eukaryotic cellular signals. Molecular dissection of their mechanisms of action has been limited in part by the lack of random mutagenesis approaches and by the complexity of signaling pathways in mammalian cells which involve multiple PKC isoforms. Here we present a rapid screen which permits the quantification of mammalian PKC activity phenotypically in the yeast Saccharomyces cerevisiae. Bovine PKC alpha cDNA is functionally expressed in S. cerevisiae. This results in a phorbol ester response: a fourfold increase in the cell doubling time and a substantial decrease in yeast colony size on agar plates. We have expressed pools of bovine PKC alpha cDNAs mutagenized by Bal 31 deletion of internal, amino-terminal, or carboxyl-terminal sequences and have identified three classes of mutants on the basis of their distinct yeast phenotypes. Representatives of each class were analyzed. An internal deletion of amino acids (aa) 172 to 225 displayed ligand-dependent but reduced catalytic activity, an amino-terminal truncation of aa 1 to 153 displayed elevated and ligand-independent activity, and a carboxyl-terminal 26-aa truncation (aa 647 to 672) lacked activity under any conditions. Additional mutations confirmed the distinct functional characteristics of these classes. Our data show that deletion of the V1 and C1 regions results in elevated basal catalytic activity which is still Ca2+ responsive. Internal deletions in the V2 and C2 regions do not abolish phorbol ester or Ca2+ regulation of PKC activity, suggesting that most of the C2 domain is not essential for phorbol ester stimulation and most of the regulatory domain is dispensable for Ca2+ regulation of PKC activity. These distinct activities od the PKC mutants correlate with a specific and proportional yeast phenotype and are quantified on agar plates by yeast colony size. This provides a phenotypic screen which is suitable to identity rare, randomly altered but active mammalian PKC mutants. It quantifies their catalytic and biological activities in response to PKC activators or inhibitors for a systematic mapping of PKC structure and function or PKC-drug interaction.

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