SIGNALING BY SRC FAMILY KINASES - LESSONS LEARNT FROM DNA TUMOR-VIRUSES

Virus replication and spreading in a host population depends on highly specific interactions of viral proteins with infected cells, resultin g in subversion of multiple cellular signal transduction pathways. For instance, viral proteins cause cell cycle progression of the infected host cell in order to establish a cellular environment favourable for virus replication. Of equal importance for successful virus propagati on is virus mediated attenuation of a host's immune response. Many of the pathways controlling these aspects of cell behaviour are regulated by cellular tyrosine kinases. One particular family of these enzymes, Src family kinases, are involved in processing signals emanating from the plasma membrane upon stimulation by growth factors, by cell subst ratum or by cell-cell contact. Two families of DNA viruses, polyoma-an d herpesviruses, encode proteins targeted at tyrosine kinases. The mid dle-T antigens expressed by mouse and hamster polyomavirus associate w ith and activate Src family tyrosine kinases. Two members of the herpe s family of DNA viruses, Epslein-Barr virus (EBV) and herpesvirus saim iri (HVS), encode proteins, LMP2A and Tip, respectively, that associat e with cellular tyrosine kinases of the Src and Syk/Zap family. Upon a ssociation with these viral proteins, the activity of these tyrosine k inases is changed resulting in altered signal output. Middle-T, LMP2A and Tip are therefore excellent tools to study the regulation of Src f amily kinases. (C) 1997 Elsevier Science Inc.