ABL1, AKT1, ARHGEF7, BAD, BCL2, BCL2L1, BTK, CASP9, CCND1, CCR2, CCR5, CD4, CD40, CDC42, CDH1, CDKN1A, CDKN1B, CDKN2A, CREB1, CTNNB1, CXCR4, E2F1, EGFR, ERBB2, FAS, FCGR2A, FRAP1, FYN, GNB3, GRB2, GSK3B, GYS1, HRAS, IGF1R, INPP5D, IRAK4, IRS1, ITGB1, ITGB3, ITK, JAK2, KCNH2, KIT, KRAS, LCK, LYN, MAP2K1, MAP3K5, MAPK1, ...MAPK14, MAPK3, MAPK8, MYC, NFKB1, NFKBIA, NOS3, PAK1, PDE3B, PDPK1, PIK3C2A, PIK3C2B, PIK3C2G, PIK3C3, PIK3CA, PIK3CB, PIK3CD, PIK3R1, PIK3R2, PIK3R4, PLCG1, PRKCA, PRKCB, PRKCD, PRKCZ, PTEN, PTK2, RAC1, RAF1, RELA, RHOA, RPS6KB1, SGK1, SH3KBP1, SHC1, SOS1, SPP1, SRC, SYK, TEC, TLR4, TNF, VAV1
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The PI3K (Phosphatidylinositde-3-Kinase) family of enzymes regulate diverse biological functions in every cell type by generating lipid second messengers that ultimately results in the mediation of cellular activities such as proliferation, differentiatio ...n, chemotaxis, survival, trafficking and glucose homeostasis. On the basis of structural similarities, the PI3K members are sub-divided into three classes; Class I, II and III. The Class I and II PI3Ks are found only in metazoa, whereas, Class III PI3Ks are also found in unicellular eukaryotes. The Class I PI3Ks are sub-divided into two groups-the Class IA and Class IB PI3Ks. Class IA PI3Ks are heterodimeric enzymes consisting of regulatory subunits (p85-Alpha, p85-Beta or p55-Gamma) and a catalytic subunit (p110-Alpha, p110-Beta or p110-Delta). There is only one catalytic subunit and one regulatory subunit for Class IB PI3K, which are known as p110-Gamma and p101, respectively. Each of the catalytic subunits associates with all of the regulatory subunits. The function of Class I PI3Ks is to catalyze the phosphorylation of the 3' hydroxyl subunit of Phosphoinositides. In vitro, all Class I PI3Ks are capable of phosphorylating PtdIns/PI (Phosphatidylinositol) to PtdIns(3)P, PtdIns(4)P/PIP (Phosphatidylinositol-4-phosphate) to PtdIns(3,4)P2 and PtdIns (4,5)P2/PIP2 (Phosphatidylinositol-4,5-bisphosphate) to PtdIns(3,4,5)P3/PIP3 (Phosphatidylinositol 3,4,5-trisphosphate), with PIP2 as the main substrate in vivo. The acronyms PIP2 and PIP3 are used to describe the substrate and product of Class I PI3Ks, respectively. The Class II PI3Ks are termed as PIK3C2Alpha (Phosphoinositide-3-Kinase-Class-2-Alpha Polypeptide), PIK3C2Beta and PIK3C2Gamma. Whereas, Class I PI3Ks reside mainly in the cytoplasm until recruited to active signaling complexes, the Class II PI3Ks are largely constitutively associated with membrane structures, including plasma membrane, intracellular membranes and somewhat surprisingly with nuclei. In vitro, Class II PI3Ks phosphorylate PtdIns and PIP, but, unlike Class I PI3Ks, not PIP2. Class II PI3Ks is not associated with a regulatory subunit. They do possess extended N- and C-termini relative to the Class I PI3Ks, which may serve this function. The Class III PI3K, PIK3C3 (Phosphoinositide-3-Kinase-Class-3) preferentially phosphorylates PtdIns to yield PtdIns (3)P, which recruits a distinct group of effector proteins with so-called FYVE or Phox (PX) domains. The catalytic subunit is complexed with a serine-threonine protein kinase, PIK3R4 (Phosphoinositide-3-Kinase-Regulatory Subunit Polypeptide-4)/p150, also known as the regulatory subunit. The major cellular function of the Class III PI3Ks is in intracellular trafficking. Class III along with Class II PI3Ks regulate various aspects of vesicle trafficking, and as such, there is an obvious potential for their involvement in activities such as antigen processing and cytotoxic responses that involve the directed sub-cellular transport of intracellular vesicles and their cargo.
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