期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：25
页码：9411-9416
DOI：10.1073/pnas.0403160101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Herpes simplex virus 1 encodes at least four genes whose functions include blocking apoptosis induced by exogenous agents (e.g., sorbitol, Fas ligand, and BAD protein) or replication-incompetent mutants (e.g., the d120 mutant lacking both copies of the {alpha}4 gene). US3, one of these four genes, encodes a serine-threonine kinase that has been demonstrated to block apoptosis induced by proapoptotic cellular proteins or by the d120 mutant. The amino acid context of serine-threonine phosphorylated by US3 is similar to that of the cAMP-dependent protein kinase PKA. We report that (i) the pattern of proteins phosphorylated by US3 in transduced cells or in cells infected with WT virus overlaps that of phosphoproteins targeted by PKA, (ii) activation of PKA blocks apoptosis induced by d120 mutant or by BAD protein independently of US3, (iii) US3 protein kinase phosphorylates peptides containing the serine or threonine targeted by PKA including that present in the regulatory type II{alpha} subunit of PKA, and (iv) in WT virus-infected cells the regulatory type II{alpha} subunit is phosphorylated in a US3-dependent manner. We conclude that a major determinant of the antiapoptotic activity of the US3 protein kinase is the phosphorylation of PKA substrates by either or both enzymes.
关键词：replication-defective viruses ; BAD protein ; forskolin ; RIIα subunit of PKA
