Adenovirus endocytosis via alpha(v) integrins requires phosphoinositide-3-OH kinase.
Integrins mediate cell adhesion and motility on the extracellular matrix, yet they also promote viral attachment and/or entry. Evidence is presented that adenovirus internalization by alpha(v) integrins requires activation of phosphoinositide-3-OH kinase (PI3K), whereas alpha(v) integrin-mediated cell motility depends on the ERK1/ERK2 mitogen-activated protein kinase pathway. Interaction of adenovirus with alpha(v), integrins induced activation of PI3K. Pharmacologic or genetic disruption of endogenous PI3K activity blocked adenovirus internalization and virus-mediated gene delivery yet had no effect on integrin-mediated cell adhesion or motility. Therefore, integrin ligation engages distinct signaling pathways that promote viral endocytosis or cell movement.
Li
E
E
Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.
Stupack
D
D
Klemke
R
R
Cheresh
D A
DA
Nemerow
G R
GR
D000260:Adenoviruses, Human / Q000187:drug effects / Q000502:physiology*; D000730:Androstadienes / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism*; D002384:Catalysis; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology; D003524:Cyclosporins; D004705:Endocytosis; D004789:Enzyme Activation; D005419:Flavonoids / Q000494:pharmacology; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D039564:Integrin alphaV; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D014407:Tumor Cells, Cultured; D000077191:Wortmannin
D000730:Androstadienes; D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D002867:Chromones; D003524:Cyclosporins; D005419:Flavonoids; D039564:Integrin alphaV; D009025:Morpholines; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C051527:cyclosporine metabolite M17; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D000077191:Wortmannin