Cell adhesion to phosphatidylserine mediated by a product of growth arrest-specific gene 6.
Gas6, a product of a growth arrest-specific gene 6, potentiates proliferation of vascular smooth muscle cells and prevents cell death of vascular smooth muscle cells. It has been also demonstrated that Gas6 is a ligand of receptor tyrosine kinases Axl, Sky, and Mer. Gas6 contains gamma-carboxyglutamic acid residues, which are found in some blood coagulation factors and mediate the interaction of the coagulation factors with negatively charged phospholipid. In this study, we clarified that Gas6 specifically bound to phosphatidylserine and the binding was dependent on Ca2+ and gamma-carboxyglutamic acid residues. Furthermore, we found that U937 cells, which express Gas6 receptor on their surfaces, adhered to phosphatidylserine-coated enzyme-linked immunosorbent assay (ELISA) plate only in the presence of Gas6 and Ca2+. U937 cells also bound to ELISA plate coated with phosphatidylinositol, but the binding was independent of Gas6 and Ca2+. On the other hand, U937 cells did not adhere to phosphatidylcholine- or phosphatidylethanolamine-coated ELISA plate even in the presence of Gas6 and Ca2+. These findings suggest that Gas6 may play a role in recognition of cells exposing phosphatidylserine on their surfaces by phagocytic cells, which is supposed to be one of the mechanisms for clearing dying cells.
Nakano
T
T
Discovery Research Laboratory II, Shionogi & Co., Ltd., 5-12-4 Sagisu, Fukushima-ku, Osaka 553, Japan. toru@shionogi.ac.jp
Ishimoto
Y
Y
Kishino
J
J
Umeda
M
M
Inoue
K
K
Nagata
K
K
Ohashi
K
K
Mizuno
K
K
Arita
H
H
D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion; D006224:Cricetinae; D004797:Enzyme-Linked Immunosorbent Assay; D036341:Intercellular Signaling Peptides and Proteins; D007700:Kinetics; D008274:Magnesium / Q000378:metabolism; D015513:Oncogene Proteins / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D014407:Tumor Cells, Cultured; D000094963:Axl Receptor Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6
D002118:Calcium; D036341:Intercellular Signaling Peptides and Proteins; D008274:Magnesium; D015513:Oncogene Proteins; D010718:Phosphatidylserines; D011506:Proteins; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases; D011956:Receptors, Cell Surface; D000094963:Axl Receptor Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6