Other molecules such as Vav contribute to PI3K activation in B cells by a mechanism that involves the activation of Rac1 which then binds to p85 through its RhoGAP domain. CD19 phosphorylation activates Lyn which in turn recruits PI3K regulatory subunit (p85). CD21 binds opsonized antigenic particles and activates complement component C3, a reaction central to complement function in the immune response and sustained BCR signaling.For B cell development, the ability of CD19 to promote a thymus-dependent immune response is linked to its capacity to recruit and activate PI3K. The co-receptor complex is also composed of CD21 and CD81. CD19 has an important, but not indispensable, role in PI3K activation as it is required for sustained PI3K activation after BCR stimulation. CD19 is one of the main regulators of PI3K activity in B cells. Engagement of BCR-antigen complex activates intracellular protein tyrosine kinases such as SYK, BTK and Fyn which phosphorylate the co-receptors CD19 and BCAP at the YXXM motifs. In B cells, PI3K is activated within seconds of antigen-receptor triggering. The Class I and III PI3Ks facilitate B cell development through defined stages, resulting in at least three distinct lineages of mature B lymphocytes. In the immune system, impaired PI3K signaling leads to immunodeficiency whereas unrestrained signaling contributes to autoimmunity and leukemia. Phosphoinositide-3-Kinases (PI3K) regulate numerous biological processes including cell growth, differentiation, survival, proliferation, migration and metabolism.
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