Figure 5

The Src family kinase (SFK) Lck is activated by the membrane phosphatase CD45 through dephosphorylation of its regulatory C-terminal tyrosine Tyr⁵⁰⁵. A significant fraction of Lck associates with rafts, yet CD45 is restricted to the nonraft membrane fraction. Raft association of Lck therefore sequesters it from CD45, leading to reduced activity for the raft-associated pool of molecules. Drug treatments that disrupt rafts, such as filipin and Lat B, eliminate this sequestration, resulting in activation of Lck [30]. Conversely, signals that activate actin polymerization and assembly of rafts, such as that from the TCR in T cells, are predicted to enhance the sequestration and down-regulation of raft-associated Lck.