SRC mediates a switch from microtubule- to actin-based motility of vaccinia virus.
The cascade of events that leads to vaccinia-induced actin polymerization requires Src-dependent tyrosine phosphorylation of the viral membrane protein A36R. We found that a localized outside-in signaling cascade induced by the viral membrane protein B5R is required to potently activate Src and induce A36R phosphorylation at the plasma membrane. In addition, Src-mediated phosphorylation of A36R regulated the ability of virus particles to recruit and release conventional kinesin. Thus, Src activity regulates the transition between cytoplasmic microtubule transport and actin-based motility at the plasma membrane.
Cell Motility Laboratory, Room 529, Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
Timothy P
TP
Newsome
Niki
N
Scaplehorn
Michael
M
Way
D000199:Actins / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism / Q000821:virology; D002645:Chickens; D016384:Consensus Sequence; D004789:Enzyme Activation; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014616:Vaccinia virus / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000378:metabolism; D015678:Viral Structural Proteins / Q000378:metabolism*; D014771:Virion / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism*
C400287:A36R protein, Vaccinia virus; D000199:Actins; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; D015678:Viral Structural Proteins; C074512:42kDa protein, Vaccinia virus; D019000:Phosphotyrosine; D019061:src-Family Kinases; D016547:Kinesins