| Cell signaling through the protein kinases cAMP-dependent protein kinase, protein kinase Cepsilon, and RAF-1 regulates amphotropic murine leukemia virus envelope protein-induced syncytium formation. | |
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MedLine Citation:
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PMID: 15741175 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Amphotropic murine leukemia virus (A-MuLV) utilizes the PiT2 sodium-dependent phosphate transporter as its cell surface receptor to infect mammalian cells. The process of A-MuLV infection requires cleavage of the R peptide from the envelope protein. This occurs within virions thereby rendering them competent to fuse with target cells. Envelope proteins lacking the inhibitory R peptide (e.g. envelope (R-) proteins) induce viral envelope-mediated cell-cell fusion (syncytium). Here we have performed studies to determine if cell signaling through protein kinases is involved in the regulation of PiT2-mediated A-MuLV envelope (R-)-induced syncytium formation. Truncated A-MuLV retroviral envelope protein lacking the inhibitory R peptide (R-) was used to induce viral envelope-mediated cell-cell fusion. Signaling through cyclic AMP to activate PKA was found to inhibit envelope-induced cell-cell fusion, whereas treatment of cells with PKA inhibitors H89, KT5720, and PKA Catalpha siRNA all enhanced this cell fusion process. It was noted that activation of PKC, as well as overexpression of PKCepsilon, up-regulated A-MuLV envelope protein-induced cell-cell fusion, whereas exposure to PKC inhibitors and expression of a kinase-inactive dominant-negative mutant of PKCepsilon (K437R) inhibited syncytium formation. v-ras transformed NIH3T3 cells were highly susceptible to A-MuLV envelope-induced cell-cell fusion, whereas expression of a dominant-negative mutant of Ras (N17Ras) inhibited this cell fusion process. Importantly, activation of Raf-1 protein kinase also is required for A-MuLV envelope-induced syncytium formation. Expression of constitutively active BXB Raf supported, whereas expression of a dominant-negative mutant of Raf-1 (Raf301) blocked, A-MuLV-induced cell-cell fusion. These results indicate that specific cell signaling components are involved in regulating PiT2-mediated A-MuLV-induced cell-cell fusion. Selective pharmacological modulation of these signaling components may be an effective means of altering cell susceptibility to viral-mediated cytopathic effects. |
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Authors:
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Wei Wang; Zsolt Jobbagy; Terry H Bird; Maribeth V Eiden; Wayne B Anderson |
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Publication Detail:
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Type: Journal Article Date: 2005-03-01 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 280 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2005 Apr |
Date Detail:
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Created Date: 2005-04-25 Completed Date: 2005-06-21 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 16772-83 Citation Subset: IM |
Affiliation:
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Laboratory of Cellular Oncology, NCI, National Institutes of Health, Bethesda, MD 20892, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blotting, Western Cell Fusion Cell Line Cricetinae Cyclic AMP / chemistry Cyclic AMP-Dependent Protein Kinases / chemistry, physiology* DNA / metabolism Enzyme Activation Enzyme Inhibitors / pharmacology Epitopes / chemistry Gene Products, env / genetics Genes, Dominant Giant Cells / metabolism Leukemia Virus, Murine / metabolism Membrane Fusion Mice NIH 3T3 Cells Peptides / chemistry Protein Kinase C / physiology* Protein Kinase C-epsilon Proto-Oncogene Proteins c-raf / metabolism, physiology* RNA, Small Interfering / metabolism Retroviridae / genetics Signal Transduction* Sodium-Phosphate Cotransporter Proteins Sodium-Phosphate Cotransporter Proteins, Type III Symporters / physiology* Time Factors Transfection Up-Regulation Viral Envelope Proteins / chemistry |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/Epitopes; 0/Gene Products, env; 0/Peptides; 0/RNA, Small Interfering; 0/Sodium-Phosphate Cotransporter Proteins; 0/Sodium-Phosphate Cotransporter Proteins, Type III; 0/Symporters; 0/Viral Envelope Proteins; 60-92-4/Cyclic AMP; 9007-49-2/DNA; EC 2.7.1.-/Prkce protein, mouse; EC 2.7.11.1/Proto-Oncogene Proteins c-raf; EC 2.7.11.11/Cyclic AMP-Dependent Protein Kinases; EC 2.7.11.13/Protein Kinase C; EC 2.7.11.13/Protein Kinase C-epsilon |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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