Viral proteins and Src family kinases:Mechanisms of pathogenicity from a“liaison dangereuse”

• 作者: Anna Maria Brunati Elena Tibaldi Giorgio Palù Mario Angelo Pagano
• 来源期刊: 世界病毒学杂志
• 学科: 医学
• 关键词: Interaction PHOSPHOTYROSINE PROLINE-RICH motif SRC HOMOLOGY 2 DOMAIN SRC HOMOLOGY 3 DOMAIN
• 年，卷（期）: 2013,（2）
• 页码范围: 71-78
• 页数: 8页
• 分类号: R979.1

摘要

To complete their life cycle and spread,viruses interfere with and gain control of diverse cellular processes,this most often occurring through interaction between viral proteins(VPs)and resident protein partners.Among the latter,Src family kinases(SFKs),a class of non-receptor tyrosine kinases that contributes to the conversion of extracellular signals into intracellular signaling cascades and is involved in virtually all cellular processes,have recently emerged as critical mediators between the cell’s infrastructure and the viral demands.In this scenario,structural or ex novo synthesized VPs are able to bind to the different domains of these enzymes through specific short linear motifs present along their sequences.Proline-rich motifs displaying the conserved minimal consensus PxxP and recognizing the SFK Src homology(SH)3 domain constitute a cardinal signature for the formation of multiprotein complexes and this interaction may promote phosphorylation of VPs by SFKs,thus creating phosphotyrosine motifs that become a docking site for the SH2 domains of SFKs or other SH2 domain-bearing signaling molecules.Importantly,the formation of these assemblies also results in a change in the activity and/or location of SFKs,and these events are critical in perturbing key signaling pathways so that viruses can utilize the cell’s machinery to their own benefit.In the light of these observations,although VPs as such,especially those with enzyme activity,are still regarded as valuable targets for therapeutic strategies,multiprotein complexes composed of viral and host cell proteins are increasingly becoming objects of investigation with a view to deeply characterize the structural aspects that favor their formation and to develop new compounds able to contrast viral diseases in an alternative manner.