The Epstein-Barr virus-encoded LMP2A and LMP2B proteins promote epithelial cell spreading and motility.
The frequent expression of latent membrane proteins LMP2A and LMP2B in Epstein Barr virus (EBV)-associated tumors suggests that these proteins play a role in EBV-induced epithelial cell growth transformation. Expression of LMP2A and LMP2B had no effect on the morphology of squamous epithelial cells in monolayer culture, but their expression was associated with an increased capacity to spread and migrate on extracellular matrix. Although the mechanisms by which LMP2A and LMP2B promote cell spreading and motility are unclear, the use of selective pharmacological inhibitors has established a role for tyrosine kinases in this phenotype but ruled out contributions of phosphatidylinositol 3-kinase, extracellular signal-regulated kinase/mitogen-activated protein kinase, and protein kinase C. The ability of LMP2B to induce a phenotype that is virtually indistinguishable from that of LMP2A suggests that regions of the LMP2 protein in addition to the cytosolic amino terminus are capable of inducing phenotypic effects in epithelial cells. Thus, rather than serving to modulate the activity of LMP2A, LMP2B may directly engage signaling pathways to influence epithelial cell behavior such as cell adhesion and motility.
Allen
Michael D
MD
Cancer Research UK Institute for Cancer Studies, University of Birmingham Medical School, Birmingham B15 2TT, United Kingdom.
Young
Lawrence S
LS
Dawson
Christopher W
CW
D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D004847:Epithelial Cells / Q000473:pathology*; D005786:Gene Expression Regulation; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D006801:Humans; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D015398:Signal Transduction; D014161:Transduction, Genetic; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D011506:Proteins; D014763:Viral Matrix Proteins; D011505:Protein-Tyrosine Kinases