The glycosylphosphatidylinositol-anchored form and the transmembrane form of CD58 associate with protein kinases.
The significance of the glycosylphosphatidylinositol (GPI) anchor is unknown. Since GPI-anchored proteins mediate signaling, it has been suggested that the GPI structure serves as a signal-transducing element. However, the division of signaling functions between transmembrane and GPI-anchored proteins is unclear. Studies of distinct membrane-anchored forms of the same protein may resolve this issue. The adhesion molecule CD58 is expressed on the cell surface in both a transmembrane and a GPI-anchored form and hence provides a useful model. We studied CD58 in the human B lymphoblastoid cell line JY. In addition to mediating adhesion, CD58 is involved in signal transduction. Incubation of JY cells with immobilized anti-CD58 Abs results in extensive tyrosine phosphorylation and in secretion of TNF-alpha. We demonstrate that CD58 is associated with protein kinase(s) and with several kinase substrates. We further demonstrate that both CD58 isoforms are involved. CD58 in JY variant cells, which express only the transmembrane form, as well as CD58 in JY variant cells, which express only the GPI-anchored form, are associated with kinase activity. This association results in a phosphorylation pattern that is common to the variant and to wild-type JY cells. Thus, these findings suggest that the capacity of GPI-anchored proteins to interact with kinases is not always dependent on the GPI anchor itself.
Itzhaky
D
D
Department of Human Microbiology, Sackler School of Medicine, Tel-Aviv University, Israel.
Raz
N
N
Hollander
N
N
D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018968:CD58 Antigens / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D017261:Glycosylphosphatidylinositols / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D011494:Protein Kinases / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*
D018968:CD58 Antigens; D017261:Glycosylphosphatidylinositols; D011494:Protein Kinases