The p15 matrix protein of moloney murine leukemia virus is a phosphotyrosine protein.
Retroviruses have been etiologically implicated with leukemia in humans and animals. Understanding the virus life cycle, the proteins and enzymes involved in its replication, is essential for developing potent anti-viral drugs. Phosphorylation of retroviral proteins may alter their shape in such a way as to increase or inhibit their biological activities and thus influence the replication and pathogenic potential of the retroviruses. In our previous work, we demonstrated that non-cytotoxic doses of tyrphostins (protein tyrosine kinase blockers) inhibit moloney murine leukemia virus (Mo-MuLV) replication in acutely and chronically infected cells. In an attempt to understand their mode of action as anti-MoMuLV drugs, we examined the possibility that a viral protein is phosphorylated in tyrosine. Indeed, in our present work, we show that the p15 matrix protein (MA) of Mo-MuLV is a phosphotyrosine protein and is the only viral protein which is phosphorylated on tyrosine. Moreover, treatment of Mo-MuLV/NIH/3T3 chronically infected cells with tyrphostin AG-555 specifically inhibits the synthesis of p15 and other viral proteins but does not affect the synthesis of cellular proteins. Our results suggest that tyrosine phosphorylation of p15 MA protein may play a pivotal role in Mo-MuLV replication.
Seri
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I
Department of Microbiology and Immunology, Cancer Research Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Priel
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E
D016475:3T3 Cells / Q000821:virology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D001597:Benzylidene Compounds / Q000494:pharmacology; D015180:Electrophoresis, Gel, Two-Dimensional; D051379:Mice; D008979:Moloney murine leukemia virus / Q000737:chemistry* / Q000187:drug effects; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000276:immunology / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D020032:Tyrphostins; D014764:Viral Proteins / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
D000998:Antiviral Agents; D001597:Benzylidene Compounds; D009570:Nitriles; D011500:Protein Synthesis Inhibitors; D020032:Tyrphostins; D014764:Viral Proteins; C095713:alpha-cyano-(3,4-dihydroxy)-N-(3-phenylpropyl)cinnamide; D019000:Phosphotyrosine