Hypothetical models of CD45RB signaling. (A) The resting cells contain small, dynamic lipid rafts, each with a limited number of associated molecules, probably including the TCR. Maybe because of the small size of the rafts, CD45 is not known to be raft-associated.51 However, (B) on activation using anti-CD45RB mAb, one hypothesis is that CD45 translocates to the raft fraction where its activity increases; thereby rafts act as signaling platforms for amplifying its phosphatase activity and also may result in the movement of its substrates out of the rafts. However, a specific induction of a faster migrating form of Lck (probably as a consequence of dual dephosphorylation) is observed in the samples in which CD45 enzymatic activity was increased by treatment with the 6G3 Ab, suggesting that the effects observed are a consequence of CD45 enzymatic activity and do not represent physical displacement of Lck from the rafts. Hence, we favor model C where (C) Ab ligation causes CD45RB to translocate into and remain in the rafts longer, thereby keeping it in the vicinity of the activated kinase and, because of its increased phosphatase activity, would result in the negative regulation of raft-specific signal transduction.
