Kinases phosphoinositide

Akt is activated by binding of plasma membrane phospholipids downstream of insulin receptors, growth and survival factor receptors in a phosphoinositide 3-kinases dependent manner. In humans, there are three genes in the Akt family Aktl, Akt2 and Akt3. Their respective fimctions are still under investigation. 

All phosphoinositides are found in the cytosolic half of the lipid bilayer of the plasma or intracellular compartment membranes (left part). The different kinases acting on phosphoinositides in mammalian cells are shown in solid lines and the phosphoinositide 3-kinases, in bold. The phosphoinositides counterpart pathways catalysed by known phosphatases are represented by dashed lines. The best known phosphatases are PTEN (Phosphatase and tensin homolog deleted on chromosome 10) and SHIP (SH2 domain-containing inositol 5-phosphatase). 

Cellular phosphoinositide concentrations are under tight control by phospholipid kinases and phosphatases. Phospholipid kinases preferentially phosphorylate distinct positions of the inositol ring and hence are subdivided into phosphoinositide 3-kinases (PI3Ks), phosphoinositide 4-kinases (Pl4Ks), and phosphoinositide 5-kinases (PI5Ks) that phosphorylate Pis on position 3, 4 and 5, respectively. In a canonical pathway, Ptdlns... 

Phospholipid Kinases. Figure 2 Classification of phosphoinositide 3-kinases. 

Yang L, Williams DE, Kim J, Demirjian L, Qasimi R 53 Ruschmann J, Cao LP, Ma K, Chung SW, Duronio V, Andersen RJ, Krystal G, Mui AL Small-molecule agonists of SHIPl inhibit the phosphoinositide 3-kinase pathway in hematopoietic cells. Blood 2007 110 1942-1949. 

Chemokine Signaling in T-Lymphocyte Migration The Role of Phosphoinositide 3-kinase... 

Key Words Chemokines GTPases phosphoinositide 3-kinase protein kinase C T lymphocytes signaling tyrosine kinases. 

The Role of Class II Phosphoinositide 3-kinases in Cell Migration... 

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Ward SG. Do phosphoinositide 3-kinases direct lymphocyte navigation Trends Immunol 2004 25(2) 67-74. 

Reif K, Okkenhaug K, Sasaki T, Penninger JM, Vanhaesebroeck B, Cyster JG. Cutting edge differential roles for phosphoinositide 3-kinases, pllOgamma and pllOdelta, in lymphocyte chemotaxis and homing. J Immunol 2004 173(4) 2236-2240. 

Nombela-Arrieta C, Lacalle RA, Montoya MC, et al. Differential requirements for DOCK2 and phosphoinositide-3-kinase gamma during T and B lymphocyte homing. Immunity 2004 21(3) 429 141. 

Cumock AP, Sotsios Y, Wright KL, Ward SG. Optimal chemotactic responses of leukemic T cells to stromal cell-derived factor-1 requires the activation of both class IA and IB phosphoinositide 3-kinases. J Immunol 2003 170(8) 4021 4030. 

Maffucci T, Cooke FT, Foster FM, Traer CJ, Fry MJ, Falasca M. Class II phosphoinositide 3-kinase defines a novel signaling pathway in cell migration. J Cell Biol 2005 169(5) 789-799. 

Domin J, Harper L, Aubyn D, et al. The class II phosphoinositide 3-kinase PI3K-C2beta regulates cell migration by a PtdIns(3)P dependent mechanism. J Cell Physiol 2005 205(3) 452 162. 

Cronshaw DG, Owen C, Brown Z, Ward SG. Activation of phosphoinositide 3-kinases by the CCR4 ligand macrophage-derived chemokine is a dispensable signal for T lymphocyte chemotaxis. J Immunol 2004 172(12) 7761-7770. 

Sotsios Y, Whittaker GC, Westwick J, Ward SG. The CXC chemokine stromal cell-derived factor activates a Gi-coupled phosphoinositide 3-kinase in T lymphocytes. J Immunol 1999 163(11) 5954—5963. 

Wang J, Zhang X, Thomas SM, et al. Chemokine receptor 7 activates phosphoinositide-3-kinase-mediated invasive and prosurvival pathways in head and neck cancer cells independent of EGER. Oncogene 2005 24 5897-5904. 

Corvera, S. and Czech, M. R, Direct targets of phosphoinositide 3-kinase products in membrane traffic and signal transduction [review], Trends Cell. Biol., 8, 442-6, 1998. 

Wymann, M. P. and Pirola, L., Structure and function of phosphoinositide 3-kinases, Biochim. Biophys. Acta, 1436, 127-150, 1998. 

Weinkove D, Neufeld TP, Twardzik T, Waterfield MD, Leevers SJ 1999 Regulation of imaginal disc cell size, cell number and organ size by Drosophila class IA phosphoinositide 3-kinase and its adaptor. Curr Biol 9 1019-1029... 

Leevers SJ, Weinkove D, MacDougall LK, Hafen E, Waterfield MD 1996 The Drosophila phosphoinositide 3-kinase DpllO promotes cell growth. EMBO J 15 6584—6594 Lehner CF 1999 The beauty of small flies. Nat Cell Biol 1 E129—130... 

Brunn, G.J., Williams, J., Sabers, C., Weiderrecht, G., Lawrence, J. C., and Abraham, R. T. (1996). Direct inhibition of the signaling functions of the mammalian target of rapamycin by the phosphoinositide 3-kinase inhibitors, wortmannin and LY294002. EMBOJ. 15, 5256-5267. 

Manning, B. D., and Cantley, L. C. (2003). United at last The tuberous sclerosis complex gene products connect the phosphoinositide 3-kinase/Akt pathway to mammalian target of rapamycin (mTOR) signaling. Biochem. Soc. Trans. 31, 573-578. 

Manning, B. D., Tee, A. R., Logsdon, M. N., Blenis, J., and Candey, L. C. (2002). Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway. Mol. Cell 10, 151—162. 

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