Thy-1, via its GPI anchor, modulates Src family kinase and focal adhesion kinase phosphorylation and subcellular localization, and fibroblast migration, in response to thrombospondin-1/hep I.
Normal fibroblast subpopulations have differential surface expression of the GPI-linked raft protein Thy-1, which correlates with differences in cellular adhesion and migration in vitro. Thrombospondin-1 (TSP-1) induces an intermediate state of adhesion in fibroblasts and other cells which facilitates migration. TSP-1 and the hep I peptide derived from the amino-terminal/heparin-binding domain of TSP-1 induce disassembly of cellular focal adhesions. Our lab previously reported that the induction of focal adhesion disassembly in fibroblasts by TSP-1 or by hep I requires surface expression of Thy-1, as well as lipid raft integrity and Src family kinase (SFK) signaling. We now report that TSP-1/hep I-induced fibroblast migration requires Thy-1 expression and FAK phosphorylation, and that following TSP-1/hep I stimulation, Thy-1 associates with FAK and SFK in a lipid raft-dependent manner. Furthermore, the GPI anchor of Thy-1, which localizes the protein to specific lipid raft microdomains, is necessary for hep I-induced FAK and SFK phosphorylation, focal adhesion disassembly, and migration. This is the first report of an association between Thy-1 and FAK. Thy-1 modulates SFK and FAK phosphorylation and subcellular localization, promoting focal adhesion disassembly and migration in fibroblasts, following exposure to TSP-1/hep I.
Rege
Tanya A
TA
Department of Cell Biology, The University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Pallero
Manuel Antonio
MA
Gomez
Claudio
C
Grenett
Hernan E
HE
Murphy-Ullrich
Joanne E
JE
Hagood
James S
JS
D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D022001:Focal Adhesions; D017261:Glycosylphosphatidylinositols / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008168:Lung / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D009842:Oligopeptides / Q000494:pharmacology*; D010766:Phosphorylation; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013347:Subcellular Fractions / Q000378:metabolism; D019700:Thrombospondin 1 / Q000494:pharmacology*; D018800:Thy-1 Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D019061:src-Family Kinases / Q000378:metabolism*
D017261:Glycosylphosphatidylinositols; C110208:Hep I peptide; D009842:Oligopeptides; D011994:Recombinant Proteins; D019700:Thrombospondin 1; D018800:Thy-1 Antigens; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019061:src-Family Kinases