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Functional roles of glycosphingolipids in signal transduction via lipid rafts

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Abstract

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.

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  1. The Tokyo Metropolitan Institute of Medical Science, Japan

    Kohji Kasahara & Yutaka Sanai

  2. Tokyo Metropolitan Organization for Medical Research, Bunkyo-ku, Tokyo, 113-8613, Japan

    Kohji Kasahara & Yutaka Sanai

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Kasahara, K., Sanai, Y. Functional roles of glycosphingolipids in signal transduction via lipid rafts. Glycoconj J 17, 153–162 (2000). https://doi.org/10.1023/A:1026576804247

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