Vaccinia virus B1R kinase interacts with JIP1 and modulates c-Jun-dependent signaling.
Viruses have to adjust to the host cell to guarantee their life cycle and survival. This aspect of the virus-host cell interaction is probably performed by viral proteins, such as serine-threonine kinases, that are present early during infection. Vaccinia virus has an early Ser-Thr kinase, B1R, which, although required for successful viral infection, is poorly characterized regarding its effects on cellular proteins, and thus, its potential contribution to pathogenesis is not known. Signaling by mitogen-activated protein kinase (MAPK) is mediated by the assembly of complexes between these kinases and the JIP scaffold proteins. To understand how vaccinia virus B1R can affect the host, its roles in the cellular signaling by MAPK complexes and c-Jun activation have been studied. Independently of its kinase activity, B1R can interact with the central region of the JIP1 scaffold protein. The B1R-JIP1 complex increases the amount of MAPK bound to JIP1; thus, MKK7 and TAK1 either bind with higher affinity or bind more stably to JIP1, while there is an increase in the phosphorylation state of JNK bound to JIP1. The functional consequence of these more stable interactions is an increase in the activity of transcription factors, such as c-Jun, that respond to these complexes. Furthermore, B1R is also able to directly phosphorylate c-Jun in residues different from those targeted by JNK and, thus, B1R can also cooperate by an independent route in c-Jun activation. Vaccinia virus B1R can thus modulate the signaling of pathways that respond to cellular stress.
Santos
Claudio R
CR
IBMCC-Centro de Investigación del Cáncer, CSIC-Universidad de Salamanca, Campus Miguel de Unamuno, E-37007 Salamanca, Spain.
Blanco
Sandra
S
Sevilla
Ana
A
Lazo
Pedro A
PA
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D002522:Chlorocebus aethiops; D004789:Enzyme Activation; D006367:HeLa Cells; D006801:Humans; D007684:Kidney Tubules / Q000166:cytology / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D015398:Signal Transduction; D014616:Vaccinia virus / Q000201:enzymology*; D014764:Viral Proteins / Q000378:metabolism*; D000099151:MAP Kinase Kinase Kinase 7
D048868:Adaptor Proteins, Signal Transducing; D020930:MAP Kinase Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D017346:Protein Serine-Threonine Kinases; D016755:Proto-Oncogene Proteins c-jun; D014764:Viral Proteins; D000099151:MAP Kinase Kinase Kinase 7; C490666:MAPK8IP1 protein, human; C074058:VB1R protein, Vaccinia virus