The Structure of PI3K

From Proteopedia

Jump to: navigation, search

Structure of PI3K

Class I PI3Ks, which are tightly regulated by tyrosine kinases, are composed of an 85kDa regulatory/adapter subunit (p85) and a 110kDa catalytic subunit (p110). [1]

Adapter Subunit

Structure of PI3K p110, (3hhm)

Drag the structure with the mouse to rotate

Additional Resources

References

  1. 1.0 1.1 Hoedemaeker FJ, Siegal G, Roe SM, Driscoll PC, Abrahams JP. Crystal structure of the C-terminal SH2 domain of the p85alpha regulatory subunit of phosphoinositide 3-kinase: an SH2 domain mimicking its own substrate. J Mol Biol. 1999 Oct 1;292(4):763-70. PMID:10525402 doi:http://dx.doi.org/10.1006/jmbi.1999.3111
  2. 2.0 2.1 2.2 2.3 2.4 2.5 2.6 Wymann MP, Pirola L. Structure and function of phosphoinositide 3-kinases. Biochim Biophys Acta. 1998 Dec 8;1436(1-2):127-50. PMID:9838078
  3. Otsu M, Hiles I, Gout I, Fry MJ, Ruiz-Larrea F, Panayotou G, Thompson A, Dhand R, Hsuan J, Totty N, et al.. Characterization of two 85 kd proteins that associate with receptor tyrosine kinases, middle-T/pp60c-src complexes, and PI3-kinase. Cell. 1991 Apr 5;65(1):91-104. PMID:1707345
  4. 4.0 4.1 Batra-Safferling R, Granzin J, Modder S, Hoffmann S, Willbold D. Structural studies of the phosphatidylinositol 3-kinase (PI3K) SH3 domain in complex with a peptide ligand: role of the anchor residue in ligand binding. Biol Chem. 2010 Jan;391(1):33-42. PMID:19919182 doi:10.1515/BC.2010.003
  5. Koch CA, Anderson D, Moran MF, Ellis C, Pawson T. SH2 and SH3 domains: elements that control interactions of cytoplasmic signaling proteins. Science. 1991 May 3;252(5006):668-74. PMID:1708916
  6. Dombrosky-Ferlan PM, Corey SJ. Yeast two-hybrid in vivo association of the Src kinase Lyn with the proto-oncogene product Cbl but not with the p85 subunit of PI 3-kinase. Oncogene. 1997 May 1;14(17):2019-24. PMID:9160881 doi:10.1038/sj.onc.1201031
  7. Weber T, Schaffhausen B, Liu Y, Gunther UL. NMR structure of the N-SH2 of the p85 subunit of phosphoinositide 3-kinase complexed to a doubly phosphorylated peptide reveals a second phosphotyrosine binding site. Biochemistry. 2000 Dec 26;39(51):15860-9. PMID:11123912
  8. Miled N, Yan Y, Hon WC, Perisic O, Zvelebil M, Inbar Y, Schneidman-Duhovny D, Wolfson HJ, Backer JM, Williams RL. Mechanism of two classes of cancer mutations in the phosphoinositide 3-kinase catalytic subunit. Science. 2007 Jul 13;317(5835):239-42. PMID:17626883 doi:317/5835/239
  9. Nolte RT, Eck MJ, Schlessinger J, Shoelson SE, Harrison SC. Crystal structure of the PI 3-kinase p85 amino-terminal SH2 domain and its phosphopeptide complexes. Nat Struct Biol. 1996 Apr;3(4):364-74. PMID:8599763
  10. 10.0 10.1 10.2 10.3 10.4 Mandelker D, Gabelli SB, Schmidt-Kittler O, Zhu J, Cheong I, Huang CH, Kinzler KW, Vogelstein B, Amzel LM. A frequent kinase domain mutation that changes the interaction between PI3Kalpha and the membrane. Proc Natl Acad Sci U S A. 2009 Oct 6;106(40):16996-7001. Epub 2009 Sep 23. PMID:19805105
  11. Dhand R, Hiles I, Panayotou G, Roche S, Fry MJ, Gout I, Totty NF, Truong O, Vicendo P, Yonezawa K, et al.. PI 3-kinase is a dual specificity enzyme: autoregulation by an intrinsic protein-serine kinase activity. EMBO J. 1994 Feb 1;13(3):522-33. PMID:8313897
  12. von Willebrand M, Williams S, Saxena M, Gilman J, Tailor P, Jascur T, Amarante-Mendes GP, Green DR, Mustelin T. Modification of phosphatidylinositol 3-kinase SH2 domain binding properties by Abl- or Lck-mediated tyrosine phosphorylation at Tyr-688. J Biol Chem. 1998 Feb 13;273(7):3994-4000. PMID:9461588
  13. 13.0 13.1 Walker EH, Perisic O, Ried C, Stephens L, Williams RL. Structural insights into phosphoinositide 3-kinase catalysis and signalling. Nature. 1999 Nov 18;402(6759):313-20. PMID:10580505 doi:10.1038/46319


Proteopedia Page Contributors and Editors (what is this?)

David Canner, Michal Harel, Hannah Campbell, Alexander Berchansky, Eran Hodis

Personal tools