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J Biol Chem, Vol. 274, Issue 32, 22591-22596, August 6, 1999
From the Zeneca Central Toxicology Laboratory, Alderley Park,
Macclesfield, Cheshire, SK10 4TJ, United Kingdom
Cross-linking MHC class II molecules human
leukocyte antigen (HLA-DR) on the surface of THP-1 cells was found to
induce their entry into the glycolipid-enriched membrane fraction
of the plasma membrane. At the cellular level, this resulted in the
synergistic co-aggregation of class II with cholera toxin, a
marker of membrane rafts. The accompanying induction of intracellular
protein tyrosine phosphorylation could be inhibited by treating cells
with methyl-
Intracellular Phosphotyrosine Induction by Major
Histocompatibility Complex Class II Requires Co-aggregation with
Membrane Rafts
-cyclodextrin, a drug that chelates membrane cholesterol
and thereby disperses membrane rafts. Signaling could also be inhibited
by treating cells with the Src-family kinase inhibitor PP1. Together,
these results show that the induced association of class II molecules with membrane rafts can contribute to their aggregation on the cell
surface and mediate an association with intracellular protein-tyrosine kinases.
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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