Regulation of p38 MAP kinase by anastellin is independent of anastellin's effect on matrix fibronectin.
Anastellin is an angiogenesis inhibitor derived from the first type III repeat of fibronectin (FN). Anastellin binds to fibronectin and promotes the polymerization of soluble fibronectin into a highly polymerized form termed superfibronectin. In addition, anastellin also causes remodeling of pre-existing fibronectin matrix and modulates cell signaling pathways in both endothelial cells and fibroblasts. In the present study, we address the relationship of anastellin's effects on fibronectin matrix to its effects on p38 MAP kinase (MAPK) activation. Using a mutant form of anastellin which binds to fibronectin matrix, but does not stimulate formation of superfibronectin, we demonstrate that the activation of p38 MAPK by anastellin is not dependent on the formation of superfibronectin. The mutant form of anastellin does stimulate matrix remodeling, but experiments using FN(-/-) cells show that the effect of anastellin on p38-MAPK activation is completely independent of fibronectin. Anastellin was able to activate p38 MAPK on cells in suspension as well as on cells null for beta1 integrins, suggesting that anastellin activity did not require ligation of integrins. These data suggest that the activation of p38 MAPK by anastellin is independent of anastellin's effects on fibronectin matrix organization.
You
Ran
R
Center for Cell Biology and Cancer Research (MC-165), Albany Medical College, 47 New Scotland Avenue, Albany, New York 12208, United States.
Klein
R Matthew
RM
Zheng
Mingzhe
M
McKeown-Longo
Paula J
PJ
D000704:Analysis of Variance; D004789:Enzyme Activation / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D005109:Extracellular Matrix / Q000378:metabolism*; D005347:Fibroblasts; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D008856:Microscopy, Fluorescence; D010446:Peptide Fragments / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D005353:Fibronectins; D010446:Peptide Fragments; C423921:anastellin; D048051:p38 Mitogen-Activated Protein Kinases