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KSHV ‐ TK : thymidine kinase or tyrosine kinase?
Author(s) -
Lagunoff Michael
Publication year - 2015
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201490843
Subject(s) - biology , adapter molecule crk , autophosphorylation , kinase , focal adhesion , tyrosine kinase , thymidine kinase , tyrosine phosphorylation , microbiology and biotechnology , phosphorylation , virology , signal transduction , virus , protein kinase a , herpes simplex virus , signal transducing adaptor protein
The thymidine kinases ( TK ) of alphaherpesviruses phosphorylate nucleosides, allowing viral replication in non‐dividing cells. They also phosphorylate acyclovir ( ACV ), a specific antiviral when modified. Despite encoding a TK homolog, Kaposi's sarcoma‐associated herpesvirus ( KSHV ), a gammaherpesvirus, is relatively immune to the effects of ACV . In this issue, Gill et al ([Gill MB, 2015]) show that rather than functioning as a thymidine kinase, the KSHV ‐ TK homolog has evolved a unique function as a tyrosine kinase that is autophosphorylated. KSHV ‐ TK autophosphorylation of three SH 2 domains leads to Crk binding and likely sequestration of Crk from focal adhesions. KSHV ‐ TK also binds to FAK with a concurrent loss of phosphorylation in the focal adhesions, leading to a loss of cell morphology and membrane blebbing. Rather than acting to create nucleotide pools for replication, the KSHV ‐ TK homolog may play a pivotal role in viral pathogenesis by altering focal adhesions and cell detachment.