We have previously identified the presence of Ras/ @entity8496 -independent constitutive activation of @entity3963 ( @entity3963 ) in the hairy cells (HCs) of @entity5734 . The aim of the present study was to characterize the signaling components involved in this activation and their relationship to the reported activation of @entity5180 . We found that both @entity5180 and @entity3963 activation in HCs are downstream of active @entity7242 and @entity7131 ( @entity7131 ). Inhibition with toxin B showed that @entity5180 plays no role in @entity3963 activation in HCs. However, toxin B inhibited @entity7242 and the @entity5180 -GEF Vav, demonstrating a positive feedback/activation of @entity7242 by @entity5180 . Treatment with specific small interfering RNA for various @entity7131 isoforms, or with @entity7131 isoform-specific inhibitors, demonstrated a central role for @entity27347 in the constitutive activation of @entity5180 and @entity3963 in HCs. @entity27347 and active @entity3963 were mutually associated and co-localized with mitochondria in HCs. Furthermore, active @entity27347 was nitrated on @entity669 , pointing to a reactive @entity26 species-dependent mechanism of activation. By being involved in activation of @entity3963 and @entity5180 , @entity27347 plays roles in both the survival of HCs and in the cytoskeletal dynamics responsible for the distinctive morphology and tissue homing of these cells. Our study therefore describes novel aspects of signaling important for the pathogenesis of @entity5734 .

Central role of protein kinase Cepsilon in constitutive activation of ERK1/2 and XXXX in the malignant cells of @entity5734 .

@entity27347 :: ('5581', 'Gene') :: ['PKCepsilon'] @entity7242 :: ('6714', 'Gene') :: ['Src', 'p60src'] @entity5734 :: ('MESH:D007943', 'Disease') :: ['hairy cell leukemia'] @entity26 :: ('MESH:D010100', 'Chemical') :: ['oxygen'] @entity3963 :: ('5594', 'Gene') :: ['extracellular signal-regulated kinase', 'ERK'] @entity7131 :: ('MESH:D020151', 'Disease') :: ['protein kinase C', 'PKC'] @entity669 :: ('CHEBI:18186', 'Chemical') :: ['tyrosine'] @entity5180 :: ('5879', 'Gene') :: ['Rac1'] @entity8496 :: ('22882', 'Gene') :: ['Raf']
@entity5180 :: (5879,Gene) :: ['Rac1']
