Functional roles of glycosphingolipids in signal transduction via lipid rafts.
The formation of glycosphingolipid (GSL)-cholesterol microdomains in cell membranes has been proposed to function as platforms for the attachment of lipid-modified proteins, such as glycosylphosphatidylinositol (GPI)-anchored proteins and src-family tyrosine kinases. The microdomains are postulated to be involved in GPI-anchored protein signaling via src-family kinase. Here, the functional roles of GSLs in signal transduction mediated by the microdomains are discussed. Antibodies against GSLs co-precipitate GPI-anchored proteins, src-family kinases and several components of the microdomains. Antibody-mediated crosslinking of GSLs, as well as that of GPI-anchored proteins, induces a rapid activation of src-family kinases and a transient increase in the tyrosine phosphorylation of several substrates. Enzymatic degradation of GSLs reduces the activation of src-family kinase and tyrosine phosphorylation by antibody-mediated crosslinking of GPI-anchored protein. Furthermore, GSLs can also modulate signal transduction of immunoreceptors and growth factor receptors in the microdomains. Thus, GSLs have important roles in signal transduction mediated by the microdomains.
Kasahara
K
K
The Tokyo Metropolitan Institute of Medical Science, Tokyo Metropolitan Organization for Medical Research, Japan. kashara@rinshoken.or.jp
Sanai
Y
Y
D000818:Animals; D051242:Caveolin 1; D022461:Caveolins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D006028:Glycosphingolipids / Q000502:physiology*; D006801:Humans; D008563:Membrane Lipids / Q000378:metabolism*; D009420:Nervous System / Q000254:growth & development; D017978:Receptors, Growth Factor / Q000378:metabolism; D012106:Research; D015398:Signal Transduction
D051242:Caveolin 1; D022461:Caveolins; D006028:Glycosphingolipids; D008563:Membrane Lipids; D017978:Receptors, Growth Factor