While Lyn has important functions in Epo receptor signaling in erythroid progen

It is clear that Lyn has important functions in numer ous hematopoietic cell types, from early stem progeni tors through to multiple lineages of the lymphoid sys tem and the myeloid system, Interestingly, while Lyn is not expressed in T cells, it can have a significant impact upon T cell function through modulating signaling in cells that interact with T cells, abt263 代理店 Within these signaling pathways it is becoming ap parent that Lyn has a dual role by both activating and inhibiting signaling pathways, thus it is aptly described as a signaling modulator, Within the non hematopoietic cells that express Lyn, its role in activating inhibiting various signals still requires further elucida tion, however, most studies so far point to it being a positive regulator, Immune diseases regulated by Lyn Lyn has unique roles in B lymphocyte signaling, mediating positive and inhibitory sig nals, as highlighted through the B cell phenotypes when Lyn is deleted, inactivated, and hyper activated in the whole animal, At the signaling level there are the expected major differences between Lyn and Lynup up mice, i.<br><br> e. reduced phosphorylation with Lyn deficiency and hyper phosphorylation with constitutively active Lyn. Dysregulation of Lyn results in antibody mediated autoimmune Adriamycin 分子量 disease, leading to speculation that Lyn may be a key component in such clinically similar dis eases, such as systemic lupus erythematosus, While there is limited evidence of a direct involvement of Lyn in SLE, the physiological similarities be tween dysregulated Lyn mice and autoimmune diseases may make these animals useful models of such human diseases.<br><br> It is very interesting to note that mice with de fective Lyn kinase activity, but still expressing Lyn protein have ABT-199 ic50 a less severe immune dysfunction phenotype than those with Lyn fully ablated, It is also becoming apparent that immune dis eases that are thought to be mediated by cells that dont express Lyn, i. e. T cells in asthma, can also be modu lated by dysregulation of Lyn, Inhibiting Lyn kinase activity could inhibit airway eosinophilia, as Lyn has im portant functions in IL 5 receptor signaling, in which it is associated with asthma, However, the cellular changes of Lyn mice would suggest they would be more prone to asthma. Indeed, when Lyn defi cient animals are challenged with an asthma induction model, they develop a persistent and more severe form of the disease than control mice, This effect may be due to the lack of inhibitory Lyn mediated signaling in the many non T cell immune regulators and mediators, i. e. B cells, macrophages, eosinophils, neutrophils, den tritic cells and mast cells, in these Lyn mice, resulting in an inability to negatively regu late Th2 immune responses.