Leukaemia Lymphoma and Lyn The level and or activity of tyr

[jy9202]

Lyn mice are viable but display defects in their im mune system, myeloid abt263 費用 lineage, erythroid com partment, and have neuronal and prostate tissue deficiencies, Mice expressing a constitutively active Lyn also develop abnormal ities of the myeloid and lymphoid systems, and our preliminary work illustrates they have erythroid ab normalities, Further investi gation is required to delineate any alterations to other tissues organs in these hyperactive Lyn expressing mice. Intriguingly, Lynup up mice do not appear more prone to developing any neoplasia, while Lyn animals have an age dependent accumulation of disseminated macro phage tumors, While much emphasis is placed on the kinase activity of Lyn, and indeed other SFK tyrosine kinases, as providing the paramount down stream sig naling capacity of this enzyme, the recent identification of major immune cell signaling differences in mice car rying kinase dead alleles of Lyn compared to those that have Lyn deleted, implies there are important scaffolding functions for this molecule in addition to its enzymatic activity.

In addition to the normal function and crucial role of Lyn in B cell receptor signaling, as well as several growth cytokine receptor signaling sys tems, it has also been noted to function in numer ous mature as well as progenitor blood cells. Adriamycin 臨床試験 While Lyn has important functions in Epo receptor signaling in erythroid progenitors, it is also the most abundant SFK in mature erythrocytes and phos phorylates important cell shape controllers ion transpor ters in these cells e. g.

Band 3, in response to physico chemical regulators of red cell function, Lyn is also involved in thrombopoietin receptor signaling in megakaryocytes, as well as in mature platelets, where it functions supplier ABT-199 in regulating integrin and FcR signaling, crucial for their function in adhesion and aggregation, Lyn has important signaling func tions in mast cells; engagement of the FcERI activates Lyn to regulate mast cell degranulation, Again, in this system as in others, Lyn appears to have both positive and negative regulatory roles. A recent study highlighted a potential isoform specific function for the two molecular species of Lyn, within platelets, utilizing a background of Lyn cells within which the specific isoforms of Lyn were then expressed either individually of in combination, Not only did LynA and LynB have differing signaling capaci ties, but they also displayed differential association with effector molecules.

Indeed to restore the wild type sig naling, both LynA and LynB isoforms needed to be co expressed, either isoform alone producing abnormal responses, Extending these isoform specific studies to the other cell systems that involve Lyn will be of great interest, and may help delineate the molecular mechan isms behind the duplicitous nature of this enzyme.