Lipid Raft and Signal Transduction. Tao Chen. Lipid Raft. A cholesterol-enriched microdomain in cell membrane. A liquid-ordered phase dispersed in a liquid disordered matrix of cell membrane, which is thought to minimize the free energy between the two phases.
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B Extracellular space or vesicle/Golgi apparatus lumen
(1)Non-raft membrane (2)Lipid raft (3)Lipid raft associated transmembrane protein (4)Non-raft membrane protein
(5)Glycosylation modifications (6)GPI-anchored protein (7)Cholesterol (8)Glycolipid
Red: chemical messenger
Yellow: transmembrane protein
Purple: cell membrane
state with lipid rafts could be activated through ligand binding
(b) Individual receptors with weak raft affinity could oligomerize on ligand binding, and this would lead to an increased residency time in rafts.
(1) Single Rafts Model
Activated receptors could recruit
cross linking proteins that bind to proteins in other
rafts, and this would result in raft coalescence.
ZAP-70 activate other proteins such as LAT, a raft-associated adaptor, through cross linking, LAT can recruit other proteins into the raft and further amplify the signal.
Cytosolic kinase Csk bind to raft-associated protein CBP and then inactivate the Src-family kinases through phosphorylation
Ligand-induced receptor dimerization of TCR/CD3
Phosphorylation of the receptor’s ITAMs by Src-family protein tyrosine kinases