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GPI-anchored proteins and acylated proteins like src-family tyrosine kinases and trimeric G proteins are known to associate with GSL microdomains. GPI-anchored proteins generally have saturated acyl chains, which are likely to insert preferentially into GSL microdomains. Src-family kinases are modified by saturated-chain lipids: palmitoylation and myristoylation, which are likely to insert preferentially into GSL microdomains.
Antibody(or ligand)-mediated crosslinking of GPI-anchored proteins induces activation of src-family kinases and transient increase in tyrosine phosphorylation of several substrates (Fig.2a). Antibody-mediated crosslinking of GSLs also induces activation of src-family kinases and transient increase in tyrosine phosphorylation (Fig.2b). This shows that antibody-mediated crosslinking of GSLs can mimic GPI-anchored protein signaling. Anti-GPI-anchored protein antibodies co-immunoprecipitate src-family kinases, and anti-GSL antibodies co-immunoprecipitate src-family kinases and GPI-anchored proteins. Furthermore, enzymatic removal of the carbohydrate moiety from cell-surface GSLs impairs activation of the src-family kinase by antibody-mediated crosslinking of GPI-anchored protein. These observations suggest that GSLs are involved in GPI-anchored protein signaling. Although there is some discussion as to whether GPI-anchored proteins associate with GSL microdomains at steady state, it is thought that antibody-mediated crosslinking of GPI-anchored proteins induces translocation to GSL microdomains or stabilizes association with GSL microdomains. | |
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References | (1) | Simons K, Toomre D : Lipid rafts and signal transduction. Nature Rev. Mol.Cell Biol. 1, 31-39, 2000 |
| (2) | Kasahara K, Sanai Y : Functional roles of glycosphingolipids in signal transduction via lipid rafts. Glycoconj. J. 17 (3-4), 153-162, 2000 |
| (3) | Kasahara, K, Sanai, Y : Glycosphingolipid microdomains / caveolae and signal transduction. (in Japanese) Protein, Nucleic Acid and Enzyme 43(16), 2522-2530, 1998 |
| (4) | Kasahara K, Watanabe K, Takeuchi K, Kaneko H, Oohira A, Yamamoto T, Sanai Y : Involvement of gangliosides in glycosylphosphatidylinositol-anchored neuronal cell adhesion molecule TAG-1 signaling in lipid rafts. J Biol Chem 275
(44), 34701-34709, 2000 |
| (5) | Kasahara, K, Watanabe, Y, Yamamoto, T, Sanai , Y : Association of src family tyrosine kinase Lyn with ganglioside GD3 in rat brain. Possible regulation of Lyn by glycosphingolipid in caveolae-like domains. J. Biol. Chem. 272(47), 29947-29953, 1997 |
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