Class 1 phosphoinositide 3-kinases

Table 4.1 Summary of the structural properties of the three classes of phosphoinositide kinases (PI 3-kinases) and their substrates...

It should be hoted that phosphatidylinositol, Ptdins, itself is not considered to be a proper phosphoinositide. Therefore, en mes which phosphorylate only Ptdins. such as the Class III PI 3-kinases. are not strictly phosphoinositide kinases, although they have sequence homologies with other PI 3-kinases and are therefore included in the superlamily of phosphoinositide kinases. This information is taken from ref. 3, with permission of the authors and Annu. Rev. Biochem. 

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

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. 

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... 

The characteristics of the four major classes of histamine receptors are summarized. Question marks indicate suggestions from the literature that have not been confirmed. AA, arachidonic acid DAG, diacylglycerol Iko,2+, calcium-activated potassium current IP3, inositol 1,4,5-trisphosphate NHE, sodium-proton exchange, PKC, protein kinase C NO, nitric oxide PTPLC, phosphoinositide-specific phospholipase C TXA2, thromboxane A2. Has brain-penetrating characteristics after systemic administration. 

Arcaro, A. Zvelebil, M.J. Wallasch, C. Ullrich, A. Waterfield, M.D. Dom-in, J. Class II phosphoinositide 3-kinases are downstream targets of activated polypeptide growth factor receptors. Mol. Cell. Biol., 20, 3817-3830 (2000)... 

Ono, F. Nakagawa, T. Saito, S. Owada, Y. Sakagami, H. Goto, K. Suzuki, M. Matsuno, S. Kondo, H. A novel class II phosphoinositide 3-kinase predominantly expressed in the liver and its enhanced expression during hver regeneration. J. Biol. Chem., 273, 7731-7736 (1998)... 

S Additional information <1, 2, 3, 4, 5, 6> (<1,2,3,4>, enzyme is involved in the synthesis of 3-phosphoinositides. Class I phosphoinositide 3-kinases are further subdivided into class lA and IB enzymes, which signal downstream of tyrosine kinase and heterotrimeric G protein-coupled receptors, respectively. All class I phosphoinositide 3-kinase members also bind to Ras, but the role of this interaction in physiological phosphoinositide 3-kinase signalling is not entirely clear [1] <1,4>, enzyme can promote proliferation [1] <1,2,3,4>, phosphoinositide 3-kinase and DNA synthesis... 

PtdIns-3-kinase C2a PtdIns-3-kinase C2/I PtdIns-3-kinase C2y class II phosphoinositide 3-kinase C2a class II phosphoinositide 3-kinase C2/I... 

S Additional information <4, 8> (<8> the class II phosphoinositide 3-ki-nase C2a is activated by clathrin and regulates clathrin-mediated membrane trafficking [9] <4> TNFa and leptin stimulate the a-isoform of class II phosphoinositide 3-kinase [5] <8> PI3K-C2cr and PI3K-C2/1 represent two downstream targets of the activated epidermal growth factor... 

Additional information <4, 8> (<4> TNFot and leptin stimulate the a-iso-form of class II phosphoinositide 3-kinase [5] <8> interaction with Grb2 dramatically increases catalytic activity. Proline-rich motifs within the N-ter-minus of PI3K-C2/1 mediate the association of this enzyme with activated EGF receptor and this interaction involves the Grb2 adaptor [14]) [5, 14]... 

Domin, J. Caidarov, I. Smith, M.E.K. Keen, J.H. Waterfield, M.D. The class II phosphoinositide 3-kinase PI3K-C2a is concentrated in the trans-Colgi network and present in clathrin-coated vesicles. J. Biol. Chem., 275, 11943-11950 (2000)... 

El Sheikh, S.S. Domin, J. Tomtitchong, P. Abel, P. Stamp, C. Lalani, E.-N. Topographical expression of class lA and class II phosphoinositide 3-kinase enzymes in normal human tissues is consistent with a role in differentiation. BMC Clin. Pathol., 3, 4-18 (2003)... 

Elis, W. et al. 2008. Down-regulation of class II phosphoinositide 3-kinase-a expression below a critical threshold induces apoptotic cell death. Mol. Cancer Res. 6, 614—623. 

PBKs phosphorylate inositol lipids at the 3 position of the inositol ring to generate the 3-phosphoinositide PI(3,4,5)P3, (PIP3). PBKs of class IB are directly activated by GP t, but others PBK also belong to pathways of receptors with or coupled to tyrosine kinase activity. PIP3 may recruit to tlie membrane various protein kinases, phosphoinositide-dependent kinase-1 (PDK-1), protein kinase B (PKB, or Akt), protein kinase (PKCQ, PLC t and cytosolic tyrosine kinases such as the Bruton s tyrosine kinase (Btk). 

ACPD receptors are linked by G-proteins to the phosphoinositide-protein kinase C (PI-PKC) and adenylate cyclase-cyclic AMP second messenger systems (Conn and Desai, 1991 Winder and Conn, 1992). Actions on the PI system promote the release of Ca from intracellular stores (Conn and Desai, 1991). The most selective agonist for ACPD receptors is lS,3R-trans-ACPD, although Glu, ibotenate and Quis also act at these receptors. A related class of metabotropic receptors is activated by APB. Seven different metabotropic Glu receptors (mGluRl-7) have been cloned to date (Hollmann and Heinemann, 1994 Saugstad et al.,... 

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