ABL1, AKT1, AKT2, AKT3, ATF2, ATF3, BCL10, BCR, BLK, BLNK, BTK, C3, CALM1, CALM2, CALM3, CAMK2A, CAMK2B, CAMK2G, CBL, CD180, CD19, CD40, CD79A, CD79B, CD81, CHUK, CR2, CREB1, DAPP1, ELK1, FCGR2B, FOS, FOXO3, FYN, HRAS, IKBKB, IKBKE, IKBKG, IL4, IL4R, INPP5D, IRS1, ITPR1, ITPR3, JUN, KRAS, LYN, MALT1, MAP2K1, MAP2K2, MA...PK1, MAPK14, MAPK3, MAPK8, MAPK9, NFAT5, NFATC1, NFATC2, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NRAS, PDPK1, PIK3AP1, PIK3C2A, PIK3C2B, PIK3C3, PIK3R1, PIK3R2, PLCB1, PLCB2, PLCG1, PLCG2, PPP3CA, PRKCB, PRKCI, PRKCZ, PTEN, PTPRC, RAC1, RAF1, REL, RELA, RELB, SPP1, SYK, TEC, TLR4, VAV1, VAV3
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PI3Ks (Phosphoinositide-3-Kinases) regulate numerous biological processes, including cell growth, differentiation, survival, proliferation, migration and metabolism. In the immune system, impaired PI3K signaling leads to immunodeficiency, whereas unrestra ...ined PI3K signaling contributes to autoimmunity and Leukemia. The Class I and III PI3Ks basically facilitate B-cell development through defined stages, resulting in at least three distinct lineages of mature B-lymphocytes. In B-cells, PI3K is activated within seconds of antigen-receptor triggering. The BCR (B-Cell antigen Receptor) plays a critical role in recognition of antigens and activation of B-cells. The BCR or mIg (Membrane Immunoglobulin) is associated with Ig-Alpha/CD79A (CD79A Antigen) and Ig-Beta/CD79B (CD79B Antigen) heterodimer. The mIg subunits bind antigen and cause receptor aggregation, while the Ig-Alpha/Ig-Beta subunits transduce signals to the cell interior. Engagement of BCR-antigen complex activates intracellular protein tyrosine kinases like SYK (Spleen Tyrosine Kinase), BTK (Bruton Agammaglobulinemia Tyrosine Kinase) and Fyn (Fyn Oncogene Related to Src, FGR, YES). These tyrosine kinases phosphorylate the co-receptors CD19 (CD19 Antigen) and BCAP (B-Cell Adaptor Protein) at the YXXM motifs, which provide binding sites for PI3Ks. CD19 is one of the main regulators of PI3K activity in B-cells. CD19 has an important, but not indispensable, role in PI3K activation rather it is required for sustained PI3K activation after BCR stimulation. The co-receptor complex is also composed of CD21 (CD21 Antigen) and CD81. CD21 binds opsinized antigenic particles and activate Complement Component-C3,a reaction central to complement function in the immune response and sustained BCR signaling. Many other transmembrane receptors are known to modulate specific elements of BCR signaling. A few of these are CD45 (CD45 Antigen) and Fc-GammaRIIB (Low Affinity Immunoglobulin Gamma Fc Region Receptor-IIB). CD45 occurs as a component of a complex of proteins associated with the antigen receptor, and may regulate signal transduction by modulating the phosphorylation state of the co-receptors like CD19.
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