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Article ; Online: A novel variant in the PTPN11 gene c.1277A>G p.(His426Arg) in a patient with Noonan Syndrome with Multiple Lentigines.

Kuo, Olivia / Molloy, Kevin / Sabir, Ataf / Fleming, Andrew / Edwards, Matthew / Morris-Rosendahl, Deborah / Fassihi, Hiva / Preston, Philip

Clinical and experimental dermatology

2024

Language	English
Publishing date	2024-04-18
Publishing country	England
Document type	Journal Article
ZDB-ID	195504-4
ISSN	1365-2230 ; 0307-6938
ISSN (online)	1365-2230
ISSN	0307-6938
DOI	10.1093/ced/llae121
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Zs.A 1278: Show issues

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Article: Effects of plant residues on C:N:P of soil, microbial biomass, and extracellular enzyme in an alpine mea-dow on the Qinghai-Tibetan Plateau, China.

Xiao, Xiang-Qian / Zhang, Hai-Kuo / Feng, Ya-Si / Wang, Ji-Peng / Liang, Chen-Fei / Chen, You-Chao / Zhu, Gao-di / Cai, Yan-Jiang

Ying yong sheng tai xue bao = The journal of applied ecology

2023 Volume 34, Issue 1, Page(s) 58–66

Abstract: Plant residues can affect C:N:P of soil, microbial biomass, and extracellular enzyme ... plant residues on the C:N:P of soil, microbial biomass, and extracellular enzyme. The results showed ... and C:P (-14.7%), microbial biomass C:P and N:P, while significantly increased microbial biomass C:N ...

Title translation	植物残体对青藏高原高寒草甸土壤、微生物和胞外酶C∶N∶P化学计量特征的影响.
Abstract	Plant residues can affect C:N:P of soil, microbial biomass, and extracellular enzyme, but the effects are still unclear. We conducted a field experiment in an alpine meadow on the eastern part of the Qinghai-Tibetan Plateau to explore the effects of removing aboveground plant or roots and adding plant residues on the C:N:P of soil, microbial biomass, and extracellular enzyme. The results showed that removing aboveground plant biomass significantly decreased soil C:N (the change was -23.7%, the same below) and C:P (-14.7%), microbial biomass C:P and N:P, while significantly increased microbial biomass C:N, and enzyme C:N:P compared with meadow without human disturbance. Removing all plant biomass (aboveground and roots) significantly reduced soil C:N (-11.6%), C:P (-24.0%), N:P (-23.3%) and microbial biomass C:N in comparison to removing aboveground plant, while significantly improved microbial biomass N:P and enzyme N:P. Adding plant residues after removing aboveground plant significantly increased microbial biomass C:N and C:P, enzyme C:N compared with removing aboveground plant, while significantly decreased enzyme N:P. Compared with removing all the plant, adding plant residues after removing whole plant significantly reduced soil C:N (-16.4%), microbial biomass C:P, N:P and enzyme N:P, while significantly increased enzyme C:N. Our results suggest that removal of plants could have a strong effect on C:N:P of soil, microbial biomass, and extracellular enzyme, and C:N:P of microbial biomass and that extracellular enzyme woule be more sensitive to plant residues. Roots could play a key role in stabilizing C:N:P of soil, microbial biomass, and extracellular enzyme under plant residues addition. Adding plant residues could be a suitable solution for restoring alpine meadows under the circumstance of intact roots, which was conducive to soil C storage, but might not be suitable for alpine meadows with serious root damage, which would increase soil CO
MeSH term(s)	Humans ; Biomass ; Tibet ; Grassland ; Soil/chemistry ; China ; Plants
Chemical Substances	Soil
Language	English
Publishing date	2023-02-17
Publishing country	China
Document type	Journal Article
ZDB-ID	2881809-X
ISSN	1001-9332
ISSN	1001-9332
DOI	10.13287/j.1001-9332.202301.008
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Article ; Online: Synergistic Effect of BiVO 4 /P-g-C 3 N 4 Heterojunction with Enhanced Optoelectronic Properties on Synthetic Colorants under Visible Light

Anuradha Chowdhury / Sridharan Balu / Kuo-Wei Lan / Louis Wei-Chih Lee / Thomas C.-K. Yang

Colorants, Vol 2, Iss 19, Pp 426-

2023 Volume 442

Abstract: ... renewable energy sources is of keen interest among researchers. In this study, we synthesize a BiVO 4 /P-g-C 3 N 4 ... colorants to evaluate the photocatalytic performances of BiVO 4 /P-g-C 3 N 4 . In addition, the chemical ... photoelectron spectroscopy and electrochemical Mott–Schottky analysis. The BiVO 4 /P-g-C 3 N 4 photocatalyst shows higher ...

Abstract	Environmental remediation in the presence of robust semiconductor photocatalysts by utilizing renewable energy sources is of keen interest among researchers. In this study, we synthesize a BiVO 4 /P-g-C 3 N 4 semiconductor heterojunction photocatalytic system through a hydrothermal route followed by utilizing a total-solvent evaporation method. The optical and electronic properties of the as-prepared heterojunction are characterized via various spectroscopic techniques. Rhodamine B (RhB) and Congo Red (CR) are used as synthetic colorants to evaluate the photocatalytic performances of BiVO 4 /P-g-C 3 N 4 . In addition, the chemical environment of the photocatalyst and its mechanistic pathways are confirmed through X-ray photoelectron spectroscopy and electrochemical Mott–Schottky analysis. The BiVO 4 /P-g-C 3 N 4 photocatalyst shows higher photodegradation (96.94%) of the mixed synthetic dyes under simulated solar-light irradiation. The as-synthesized BiVO 4 /P-g-C 3 N 4 heterojunction significantly promotes the quick separation of photoexcited carriers due to the excellent synergetic properties, the extended light absorption, and the photoelectrochemical response. Furthermore, a possible type-II charge transfer mechanism is adopted for the BiVO 4 /P-g-C 3 N 4 system after investigating the band potentials, active species, and charge carrier migration over the heterojunction interface.
Keywords	BiVO 4 ; P-g-C 3 N 4 ; heterojunction ; synthetic colorants ; photocatalysis ; environmental remediation ; Chemistry ; QD1-999
Subject code	290
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: miR-145-5p targets paxillin to attenuate angiotensin II-induced pathological cardiac hypertrophy via downregulation of Rac 1, pJNK, p-c-Jun, NFATc3, ANP and by Sirt-1 upregulation.

Lin, Kuan-Ho / Kumar, V Bharath / Shanmugam, Tamilselvi / Shibu, Marthandam Asokan / Chen, Ray-Jade / Kuo, Chia-Hua / Ho, Tsung-Jung / Padma, V Vijaya / Yeh, Yu-Lan / Huang, Chih-Yang

Molecular and cellular biochemistry

2021 Volume 476, Issue 9, Page(s) 3253–3260

Abstract: ... inhibited activation of Rac-1/ JNK /c-jun/ NFATc3 and ANP expression and induced SIRT1 expression in Ang-II ... by targeting paxillin and through modulating Rac-1/ JNK /c-jun/ NFATc3/ ANP / Sirt1 signaling ...

Abstract	Pathological cardiac hypertrophy is associated with many diseases including hypertension. Recent studies have identified important roles for microRNAs (miRNAs) in many cardiac pathophysiological processes, including the regulation of cardiomyocyte hypertrophy. However, the role of miR-145-5p in the cardiac setting is still unclear. In this study, H9C2 cells were overexpressed with microRNA-145-5p, and then treated with Ang-II for 24 h, to study the effect of miR-145-5p on Ang-II-induced myocardial hypertrophy in vitro. Results showed that Ang-II treatment down-regulated miR-145-5p expression were revered after miR-145-5p overexpression. Based on results of bioinformatics algorithms, paxillin was predicted as a candidate target gene of miR-145-5p, luciferase activity assay revealed that the luciferase activity of cells was substantial downregulated the following co-transfection with wild paxillin 3'UTR and miR-145-5p compared to that in scramble control, while the inhibitory effect of miR-145-5p was abolished after transfection of mutant paxillin 3'UTR. Additionally, overexpression of miR-145-5p markedly inhibited activation of Rac-1/ JNK /c-jun/ NFATc3 and ANP expression and induced SIRT1 expression in Ang-II treated H9c2 cells. Jointly, our study suggested that miR-145-5p inhibited cardiac hypertrophy by targeting paxillin and through modulating Rac-1/ JNK /c-jun/ NFATc3/ ANP / Sirt1 signaling, therefore proving novel downstream molecular pathway of miR-145-5p in cardiac hypertrophy.
MeSH term(s)	Angiotensin II/toxicity ; Animals ; Atrial Natriuretic Factor/genetics ; Atrial Natriuretic Factor/metabolism ; Cardiomegaly/chemically induced ; Cardiomegaly/drug therapy ; Cardiomegaly/metabolism ; Cardiomegaly/pathology ; Cells, Cultured ; Gene Expression Regulation/drug effects ; MAP Kinase Kinase 4/genetics ; MAP Kinase Kinase 4/metabolism ; MicroRNAs/genetics ; Myoblasts, Cardiac/drug effects ; Myoblasts, Cardiac/metabolism ; Myoblasts, Cardiac/pathology ; NFATC Transcription Factors/genetics ; NFATC Transcription Factors/metabolism ; Paxillin/antagonists & inhibitors ; Proto-Oncogene Proteins c-jun/genetics ; Proto-Oncogene Proteins c-jun/metabolism ; Rats ; Sirtuin 1/genetics ; Sirtuin 1/metabolism ; Vasoconstrictor Agents/toxicity ; rac1 GTP-Binding Protein/genetics ; rac1 GTP-Binding Protein/metabolism
Chemical Substances	MIRN145 microRNA, rat ; MicroRNAs ; NFATC Transcription Factors ; Paxillin ; Proto-Oncogene Proteins c-jun ; Pxn protein, rat ; Vasoconstrictor Agents ; Angiotensin II (11128-99-7) ; Atrial Natriuretic Factor (85637-73-6) ; MAP Kinase Kinase 4 (EC 2.7.12.2) ; Sirt1 protein, rat (EC 3.5.1.-) ; Sirtuin 1 (EC 3.5.1.-) ; Rac1 protein, rat (EC 3.6.1.-) ; rac1 GTP-Binding Protein (EC 3.6.5.2)
Language	English
Publishing date	2021-04-22
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	184833-1
ISSN	1573-4919 ; 0300-8177
ISSN (online)	1573-4919
ISSN	0300-8177
DOI	10.1007/s11010-021-04100-w
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Zs.A 892: Show issues

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Article ; Online: Nickel-Catalyzed C-P cross-coupling by C-CN bond cleavage.

Sun, Meng / Zhang, Hong-Yu / Han, Qi / Yang, Kuo / Yang, Shang-Dong

Chemistry (Weinheim an der Bergstrasse, Germany)

2011 Volume 17, Issue 35, Page(s) 9566–9570

Language	English
Publishing date	2011-08-22
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1478547-x
ISSN	1521-3765 ; 0947-6539
ISSN (online)	1521-3765
ISSN	0947-6539
DOI	10.1002/chem.201101930
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Article ; Online: C-reactive protein inhibits endothelium-dependent NO-mediated dilation in coronary arterioles by activating p38 kinase and NAD(P)H oxidase.

Qamirani, Erion / Ren, Yi / Kuo, Lih / Hein, Travis W

Arteriosclerosis, thrombosis, and vascular biology

2005 Volume 25, Issue 5, Page(s) 995–1001

Abstract: Objective: Elevated levels of C-reactive protein (CRP), a proinflammatory marker, are associated ... whether proinflammatory signaling pathways such as stress-activated protein kinases (p38 and c-Jun N-terminal kinase [JNK ... tetramethylpiperidine-1-oxyl (TEMPOL), NAD(P)H oxidase inhibitor apocynin, or p38 kinase (an upstream activator ...

Abstract	Objective: Elevated levels of C-reactive protein (CRP), a proinflammatory marker, are associated with reduced systemic endothelium-dependent NO-mediated dilation in patients with coronary artery disease; however, the direct effect of CRP on coronary microvascular reactivity remains unknown. Herein, we examined whether CRP can modulate endothelium-dependent NO-mediated dilation of coronary arterioles and whether proinflammatory signaling pathways such as stress-activated protein kinases (p38 and c-Jun N-terminal kinase [JNK]) and oxidative stress are involved in the CRP-mediated effect. Methods and results: Porcine coronary arterioles were isolated and pressurized without flow for in vitro study. Intraluminal treatment with a clinically relevant concentration of CRP (7 microg/mL; 1 hour) significantly attenuated the NO release and vasodilation to serotonin. Further incubation with the NO precursor l-arginine (3 mmol/L) partially restored serotonin-induced vasodilation. In the presence of superoxide scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL), NAD(P)H oxidase inhibitor apocynin, or p38 kinase (an upstream activator of NAD(P)H oxidase) inhibitor SB203850, but not xanthine oxidase inhibitor allopurinol or JNK inhibitor SP600125, the detrimental effect of CRP on serotonin-induced dilation was prevented. Dihydroethidium staining showed that CRP produced SB203850- and TEMPOL-sensitive superoxide production in the arteriolar endothelium. CRP treatment of coronary arterioles significantly increased NAD(P)H oxidase activity. Conclusions: CRP inhibits endothelium-dependent NO-mediated dilation in coronary arterioles by producing superoxide from NAD(P)H oxidase via p38 kinase activation. By impairing endothelium-dependent NO-mediated vasoreactivity, CRP could facilitate the initiation of numerous cardiovascular diseases.
MeSH term(s)	Animals ; Arterioles/drug effects ; Arterioles/enzymology ; C-Reactive Protein/pharmacology ; Coronary Vessels/drug effects ; Coronary Vessels/enzymology ; Endothelium, Vascular/drug effects ; Endothelium, Vascular/enzymology ; Female ; In Vitro Techniques ; JNK Mitogen-Activated Protein Kinases/metabolism ; Male ; Membrane Transport Proteins/genetics ; Membrane Transport Proteins/metabolism ; NADPH Oxidases/genetics ; NADPH Oxidases/metabolism ; Nitric Oxide/metabolism ; Phosphoproteins/genetics ; Phosphoproteins/metabolism ; Serotonin/pharmacology ; Serotonin Agents/pharmacology ; Superoxides/metabolism ; Swine ; Vasodilation/drug effects ; Vasodilation/physiology ; Xanthine Oxidase/metabolism ; p38 Mitogen-Activated Protein Kinases/metabolism
Chemical Substances	Membrane Transport Proteins ; Phosphoproteins ; Serotonin Agents ; Superoxides (11062-77-4) ; Nitric Oxide (31C4KY9ESH) ; Serotonin (333DO1RDJY) ; C-Reactive Protein (9007-41-4) ; Xanthine Oxidase (EC 1.17.3.2) ; NADPH Oxidases (EC 1.6.3.-) ; CYBA protein, human (EC 1.6.3.1) ; JNK Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; p38 Mitogen-Activated Protein Kinases (EC 2.7.11.24)
Language	English
Publishing date	2005-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	1221433-4
ISSN	1524-4636 ; 1079-5642
ISSN (online)	1524-4636
ISSN	1079-5642
DOI	10.1161/01.ATV.0000159890.10526.1e
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Article: Identification of specific sites in human P-glycoprotein phosphorylated by protein kinase C.

Chambers, T C / Pohl, J / Raynor, R L / Kuo, J F

The Journal of biological chemistry

1993 Volume 268, Issue 7, Page(s) 4592–4595

Abstract: Phosphorylation of P-glycoprotein (Pgp) by protein kinase C occurs on apparently the same sites ... were incubated with purified protein kinase C and [gamma-32P]ATP, and Pgp (containing 1 mol ... on serine residues. Phosphopeptides were generated by digestion with Lys-C endoproteinase or trypsin ...

Abstract	Phosphorylation of P-glycoprotein (Pgp) by protein kinase C occurs on apparently the same sites in vitro and in intact cells (in situ) and is implicated in modulation of Pgp function. The region of the molecule which contains the in vitro phosphorylation sites and two specific sites within this region are now determined by peptide sequencing. Membrane vesicles from multidrug-resistant human KB-V1 cells were incubated with purified protein kinase C and [gamma-32P]ATP, and Pgp (containing 1 mol of phosphate/mol of protein) was purified to apparent homogeneity. Phosphorylation occurred exclusively on serine residues. Phosphopeptides were generated by digestion with Lys-C endoproteinase or trypsin, partially purified by high performance liquid chromatography, and further purified with strategies developed for individual phosphopeptides. Sequence analysis by Edman degradation and comparison with the deduced amino acid sequence of human (mdr 1) Pgp identified serines 661 and 671, and one or more of serines 667, 675, and 683, as sites of phosphorylation. These sites are clustered in the linker region located between the two homologous halves of Pgp. Our results identify a previously undefined, phosphorylatable domain of Pgp, smaller in size but analogous in location to the R-domain of the cystic fibrosis transmembrane conductance regulator. These data provide a basis for a better understanding of the role of phosphorylation in the mechanism of action and regulation of this important multidrug pump protein.
MeSH term(s)	ATP Binding Cassette Transporter, Subfamily B, Member 1 ; Amino Acid Sequence ; Drug Resistance ; Humans ; Membrane Glycoproteins/chemistry ; Membrane Glycoproteins/metabolism ; Molecular Sequence Data ; Phosphorylation ; Protein Kinase C/metabolism ; Serine/metabolism ; Tumor Cells, Cultured
Chemical Substances	ATP Binding Cassette Transporter, Subfamily B, Member 1 ; Membrane Glycoproteins ; Serine (452VLY9402) ; Protein Kinase C (EC 2.7.11.13)
Language	English
Publishing date	1993-03-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
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Uc I Zs.108: Show issues

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Article: Sequence of the genome of lactate dehydrogenase-elevating virus: heterogenicity between strains P and C.

Palmer, G A / Kuo, L / Chen, Z / Faaberg, K S / Plagemann, P G

Virology

1995 Volume 209, Issue 2, Page(s) 637–642

Abstract: ... nucleotides that give rise to apparent transient reading frame differences between the LDV-P and LDV-C genomes ... LDV-C products were the same as in the LDV-P rather than the reported LDV-C genome ... The predicted LDV-P proteins, however, differed from those predicted for the LDV-C proteins between 25 ...

Abstract	The complete nucleotide sequence of genomic RNA (14104 nt) of one strain of lactate dehydrogenase-elevating virus (LDV), LDV-P, is reported. It exhibits only about 80% nucleotide identity with the sequence reported for another LDV strain, LDV-C (Godeny et al., Virology 194, 585-596 (1993), and is 68 nucleotides shorter than the reported LDV-C sequence. The difference in length is largely due to the lack of a 59-nucleotide-long direct repeat in ORF 1a of the reported LDV-C sequence. Sequence analysis of a total of 1.4 kb of ORF 1a of LDV-C via reverse transcription/polymerase chain reaction (RT/PCR) technology failed to confirm the presence of this repeat in the LDV-C genome as well as of 24 deletions/insertions of single nucleotides that give rise to apparent transient reading frame differences between the LDV-P and LDV-C genomes and might have represented frameshift mutations. An additional 35 nucleotides in ORF 1a of the RT/PCR LDV-C products were the same as in the LDV-P rather than the reported LDV-C genome. The nucleotide sequences of the 5' leader and the 3' noncoding ends of the two genomes and the heptanucleotides involved in joining the 5' leader to the bodies of the subgenomic mRNAs were highly conserved or identical. The predicted LDV-P proteins, however, differed from those predicted for the LDV-C proteins between 25% for the ORF 2 protein and 1% for the ORF 7 nucleocapsid protein. All functional motifs of the ORF 1a and ORF 1b proteins were conserved. The ORF 1a protein possesses 11 potential transmembrane segments that flank the serine protease domain.
MeSH term(s)	Amino Acid Sequence ; Base Sequence ; DNA Primers ; Genome, Viral ; Lactate dehydrogenase-elevating virus/classification ; Lactate dehydrogenase-elevating virus/genetics ; Molecular Sequence Data ; Open Reading Frames ; Polymerase Chain Reaction ; Repetitive Sequences, Nucleic Acid ; Restriction Mapping ; Sequence Homology, Amino Acid ; Sequence Homology, Nucleic Acid ; Species Specificity
Chemical Substances	DNA Primers
Language	English
Publishing date	1995-06-01
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	200425-2
ISSN	1096-0341 ; 0042-6822
ISSN (online)	1096-0341
ISSN	0042-6822
DOI	10.1006/viro.1995.1296
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Article: Human leukemia K562 cell mutant (K562/OA200) selected for resistance to okadaic acid (protein phosphatase inhibitor) lacks protein kinase C-epsilon, exhibits multidrug resistance phenotype, and expresses drug pump P-glycoprotein.

Zheng, B / Chambers, T C / Raynor, R L / Markham, P N / Gebel, H M / Vogler, W R / Kuo, J F

The Journal of biological chemistry

1994 Volume 269, Issue 16, Page(s) 12332–12338

Abstract: ... of PP1 and PP2A were unchanged in the mutant. Protein kinase C (PKC) assays and immunoblot analysis ... and furthermore, overexpressed the verapamil-sensitive drug pump P-glycoprotein at both the protein ...

Abstract	A human leukemia K562 cell mutant (K562/OA200) selected for resistance to okadaic acid (OA), an inhibitor of protein phosphatases 1 and 2A (PP1/PP2A), has been established. In wild type cells, the cytotoxicity of OA was associated with mitotic arrest and concentration- and time-dependent DNA fragmentation, a hallmark of apoptosis. The mutant was 100-fold more resistant to OA in terms of effects on these parameters. Although the synthesis of several proteins was altered, enzyme assay and immunoblot analysis indicated that the levels of PP1 and PP2A were unchanged in the mutant. Protein kinase C (PKC) assays and immunoblot analysis of calcium-dependent (cPKC) and calcium-independent (nPKC) isoforms revealed that nPKC-epsilon was strikingly absent in the mutant, which otherwise expressed in comparable amounts all other isotypes (cPKC-alpha, cPKC-beta, and nPKC-zeta) also present in the wild type. Northern blot analysis confirmed an absence of PKC-epsilon mRNA in the mutant cells. The OA200 cells were cross-resistant not only to another PP1/PP2A inhibitor, calyculin A, but also to structurally unrelated anticancer drugs (such as vinblastine and taxol) and furthermore, overexpressed the verapamil-sensitive drug pump P-glycoprotein at both the protein and mRNA levels. The mutant, however, was not cross-resistant to several PKC inhibitors tested including cardiotoxin, mastoparan, staurosporine, and an alkylphospholipid. Cardiotoxin, at a subtoxic concentration, enhanced by 6-fold vinblastine cytotoxicity in OA200 cells. These findings indicate that the multidrug resistance phenotype can be induced by cytotoxic agents other than conventional anticancer drugs, show that the development of multidrug resistance is not necessarily associated with increased cPKC activity, and identify certain PKC inhibitors that have potential as resistance modulators.
MeSH term(s)	ATP Binding Cassette Transporter, Subfamily B, Member 1 ; Antineoplastic Agents/toxicity ; Blotting, Western ; Carcinogens/toxicity ; Carrier Proteins/biosynthesis ; Cell Division/drug effects ; Clone Cells ; Cobra Cardiotoxin Proteins/toxicity ; Dose-Response Relationship, Drug ; Drug Resistance/physiology ; Ethers, Cyclic/toxicity ; Humans ; Isoenzymes/biosynthesis ; Isoenzymes/deficiency ; Isoenzymes/metabolism ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Membrane Glycoproteins/biosynthesis ; Okadaic Acid ; Phenotype ; Phosphoprotein Phosphatases/antagonists & inhibitors ; Poly A/analysis ; Poly A/metabolism ; Protein Kinase C/biosynthesis ; Protein Kinase C/deficiency ; Protein Kinase C/metabolism ; RNA/analysis ; RNA/metabolism ; RNA, Messenger ; Tumor Cells, Cultured ; Vinblastine/toxicity
Chemical Substances	ATP Binding Cassette Transporter, Subfamily B, Member 1 ; Antineoplastic Agents ; Carcinogens ; Carrier Proteins ; Cobra Cardiotoxin Proteins ; Ethers, Cyclic ; Isoenzymes ; Membrane Glycoproteins ; RNA, Messenger ; Okadaic Acid (1W21G5Q4N2) ; Poly A (24937-83-5) ; Vinblastine (5V9KLZ54CY) ; RNA (63231-63-0) ; Protein Kinase C (EC 2.7.11.13) ; Phosphoprotein Phosphatases (EC 3.1.3.16)
Language	English
Publishing date	1994-04-22
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
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Article: Phosphorylation by protein kinase C and cyclic AMP-dependent protein kinase of synthetic peptides derived from the linker region of human P-glycoprotein.

Chambers, T C / Pohl, J / Glass, D B / Kuo, J F

The Biochemical journal

1994 Volume 299 Pt 1, Page(s) 309–315

Abstract: Specific sites in the linker region of human P-glycoprotein phosphorylated by protein kinase C (PKC ... 683 was PKA-specific. Further studies showed that PG-2 acted as a competitive substrate for the P ... phosphorylated PG-2 mainly on Ser-661, Ser-667 and Ser-671. These results show that human P-glycoprotein can be ...

Abstract	Specific sites in the linker region of human P-glycoprotein phosphorylated by protein kinase C (PKC) were identified by means of a synthetic peptide substrate, PG-2, corresponding to residues 656-689 from this region of the molecule. As PG-2 has several sequences of the type recognized by the cyclic AMP-dependent protein kinase (PKA), PG-2 was also tested as a substrate for PKA. PG-2 was phosphorylated by purified PKC in a Ca2+/phospholipid-dependent manner, with a Km of 1.3 microM, and to a maximum stoichiometry of 2.9 +/- 0.1 mol of phosphate/mol of peptide. Sequence analysis of tryptic fragments of PG-2 phosphorylated by PKC identified Ser-661, Ser-667 and Ser-671 as the three sites of phosphorylation. PG-2 was also found to be phosphorylated by purified PKA in a cyclic AMP-dependent manner, with a Km of 21 microM, and to a maximum stoichiometry of 2.6 +/- 0.2 mol of phosphate/mol of peptide. Ser-667, Ser-671 and Ser-683 were phosphorylated by PKA. Truncated peptides of PG-2 were utilized to confirm that Ser-661 was PKC-specific and Ser-683 was PKA-specific. Further studies showed that PG-2 acted as a competitive substrate for the P-glycoprotein kinase present in membranes from multidrug-resistant human KB cells. The membrane kinase phosphorylated PG-2 mainly on Ser-661, Ser-667 and Ser-671. These results show that human P-glycoprotein can be phosphorylated by at least two protein kinases, stimulated by different second-messenger systems, which exhibit both overlapping and unique specificities for phosphorylation of multiple sites in the linker region of the molecule.
MeSH term(s)	ATP Binding Cassette Transporter, Subfamily B, Member 1 ; Amino Acid Sequence ; Carrier Proteins/chemical synthesis ; Carrier Proteins/metabolism ; Cell Membrane/enzymology ; Cells, Cultured ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Drug Resistance ; Humans ; Membrane Glycoproteins/chemical synthesis ; Membrane Glycoproteins/metabolism ; Molecular Sequence Data ; Peptide Fragments/chemical synthesis ; Peptide Fragments/metabolism ; Peptide Mapping ; Phosphorylation ; Protein Kinase C/metabolism ; Substrate Specificity
Chemical Substances	ATP Binding Cassette Transporter, Subfamily B, Member 1 ; Carrier Proteins ; Membrane Glycoproteins ; Peptide Fragments ; Cyclic AMP-Dependent Protein Kinases (EC 2.7.11.11) ; Protein Kinase C (EC 2.7.11.13)
Language	English
Publishing date	1994-04-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	2969-5
ISSN	1470-8728 ; 0264-6021 ; 0006-2936 ; 0306-3275
ISSN (online)	1470-8728
ISSN	0264-6021 ; 0006-2936 ; 0306-3275
DOI	10.1042/bj2990309
Database	MEDical Literature Analysis and Retrieval System OnLINE

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