Mitogenesis, cell migration, and loss of focal adhesions induced by tenascin-C interacting with its cell surface receptor, annexin II.
In a previous study we demonstrated that the alternatively spliced region of tenascin-C, TNfnA-D, bound with high affinity to a cell surface receptor, annexin II. In the present study we demonstrate three changes in cellular activity that are produced by adding intact tenascin-C or TNfnA-D to cells, and we show that all three activities are blocked by antibodies against annexin II. 1) TNfnA-D added to confluent endothelial cells induced loss of focal adhesions. 2) TNfnA-D produced a mitogenic response of confluent, growth-arrested endothelial cells in 1% serum. TNfnA-D stimulated mitogenesis only when it was added to cells before or during exposure to other mitogens, such as basic fibroblast growth factor or serum. Thus the effect of TNfnA-D seems to be to facilitate the subsequent response to growth factors. 3) TNfnA-D enhanced cell migration in a cell culture wound assay. Antibodies to annexin II blocked all three cellular responses to TNfnA-D. These data show that annexin II receptors on endothelial cells mediate several cell regulatory functions attributed to tenascin-C, potentially through modulation of intracellular signalling pathways.
Chung
C Y
CY
Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Murphy-Ullrich
J E
JE
Erickson
H P
HP
D000818:Animals; D017306:Annexin A2 / Q000276:immunology / Q000494:pharmacology; D000906:Antibodies / Q000494:pharmacology; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects*; D002455:Cell Division; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000166:cytology; D006133:Growth Substances / Q000494:pharmacology; D008934:Mitogens / Q000096:biosynthesis*; D011956:Receptors, Cell Surface / Q000502:physiology*; D019063:Tenascin / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D017306:Annexin A2; D000906:Antibodies; D006133:Growth Substances; D008934:Mitogens; D011956:Receptors, Cell Surface; D019063:Tenascin