@entity6985 induces lipid raft assembly to enhance erythropoietin receptor signaling in XXXX progenitors.

@entity1 @entity18226 @entity417 @entity5859 @entity2590 @entity1195 @entity4016 @entity6985 @entity11715
@entity417 remains the principal management challenge for @entity1 with lower risk @entity2590 ( @entity2590 ). Despite appropriate cytokine production and cellular receptor display, @entity5859 ( @entity5859 ) signaling is impaired. We reported that @entity5859 signaling is dependent upon receptor localization within lipid raft microdomains, and that disruption of raft integrity abolishes signaling capacity. Here, we show that @entity2590 erythroid progenitors display markedly diminished raft assembly and smaller raft aggregates compared to normal controls (p=0.005, raft number; p=0.023, raft size). Because @entity6985 triggers raft coalescence in T-lymphocytes promoting immune synapse formation, we assessed effects of @entity6985 on raft assembly in @entity2590 erythroid precursors and @entity1 cells. @entity6985 treatment rapidly induced lipid raft formation accompanied by @entity5859 recruitment into raft fractions together with @entity11715 , @entity4016 , and @entity18226 kinase. The @entity4016 phosphatase, @entity1195 , a key negative regulator of @entity5859 signaling, was displaced from raft fractions. @entity6985 treatment prior to Epo stimulation enhanced both @entity4016 and @entity11715 phosphorylation in UT7 and primary @entity2590 erythroid progenitors, accompanied by increased @entity11715 DNA binding in @entity1 cells, and increased erythroid colony forming capacity in both @entity1 and primary cells. Raft induction was associated with F-actin polymerization, which was blocked by Rho kinase inhibition. These data indicate that deficient raft integrity impairs @entity5859 signaling, and provides a novel strategy to enhance @entity5859 signal fidelity in non-del(5q) @entity2590 .
