Structure of Lipid Kinase p110β/p85β Elucidates an Unusual SH2-Domain-Mediated Inhibitory Mechanism

Molecular Cell

Volumn 41, Issue 5, 2011, Pages 567-578

  Zhang, Xuxiao ^a   Vadas, Oscar ^a   Perisic, Olga ^a   Anderson, Karen E ^b   Clark, Jonathan ^c   Hawkins, Phillip T ^b   Stephens, Len R ^b   Williams, Roger L ^a  

^a MRC LABORATORY OF MOLECULAR BIOLOGY   (United Kingdom)

^b BABRAHAM INSTITUTE   (United Kingdom)

^c Babraham Bioscience Technologies Ltd   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

PHOSPHOPEPTIDE; PROTEIN P110; PROTEIN P110 BETA; PROTEIN P85; PROTEIN P85 BETA; PROTEIN SH2; UNCLASSIFIED DRUG;

ARTICLE; BINDING SITE; CARBOXY TERMINAL SEQUENCE; CELL GROWTH; CRYSTAL STRUCTURE; ENZYME ACTIVE SITE; ENZYME ACTIVITY; HUMAN; MUTAGENESIS; NONHUMAN; PROTEIN DOMAIN; PROTEIN MOTIF;

AMINO ACID MOTIFS; ANIMALS; BINDING SITES; CLASS IA PHOSPHATIDYLINOSITOL 3-KINASE; GENE EXPRESSION REGULATION, ENZYMOLOGIC; HUMANS; HYDROGEN BONDING; INSECTS; MICE; MUTAGENESIS; MUTATION; PHOSPHORYLATION; PROTEIN CONFORMATION; PROTEIN STRUCTURE, TERTIARY; SRC HOMOLOGY DOMAINS;

EID: 79951993684     PISSN: 10972765     EISSN: 10974164     Source Type: Journal    
DOI: 10.1016/j.molcel.2011.01.026     Document Type: Article

References (54)

1. Backer J.M., Myers M.G.J., Shoelson S.E., Chin D.J., Sun X.J., Miralpeix M., Hu P., Margolis B., Skolnik E.Y., Schlessinger J., et al. Phosphatidylinositol 3'-kinase is activated by association with IRS-1 during insulin stimulation. EMBO J. 1992, 11:3469-3479.
2. Bae J.H., Lew E.D., Yuzawa S., Tomé F., Lax I., Schlessinger J. The selectivity of receptor tyrosine kinase signaling is controlled by a secondary SH2 domain binding site. Cell 2009, 138:514-524.
3. Beeton C.A., Chance E.M., Foukas L.C., Shepherd P.R. Comparison of the kinetic properties of the lipid- and protein-kinase activities of the p110alpha and p110beta catalytic subunits of class-Ia phosphoinositide 3-kinases. Biochem. J. 2000, 350:353-359.
4. Berndt A., Miller S., Williams O., Le D.D., Houseman B.T., Pacold J.I., Gorrec F., Hon W.C., Liu Y., Rommel C., et al. The p110 delta structure: mechanisms for selectivity and potency of new PI(3)K inhibitors. Nat. Chem. Biol. 2010, 6:117-124.
5. Bondeva T., Pirola L., Bulgarelli-Leva G., Rubio I., Wetzker R., Wymann M.P. Bifurcation of lipid and protein kinase signals of PI3Kgamma to the protein kinases PKB and MAPK. Science 1998, 282:293-296.
6. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 2008, 455:1061-1068. Cancer Genome Atlas Research Network.
7. Carpenter C.L., Duckworth B.C., Auger K.R., Cohen B., Schaffhausen B.S., Cantley L.C. Purification and characterization of phosphoinositide 3-kinase from rat liver. J. Biol. Chem. 1990, 265:19704-19711.
8. Carpenter C.L., Auger K.R., Chanudhuri M., Yoakim M., Schaffhausen B., Shoelson S., Cantley L.C. Phosphoinositide 3-kinase is activated by phosphopeptides that bind to the SH2 domains of the 85-kDa subunit. J. Biol. Chem. 1993, 268:9478-9483.
9. Chan T.O., Rodeck U., Chan A.M., Kimmelman A.C., Rittenhouse S.E., Panayotou G., Tsichlis P.N. Small GTPases and tyrosine kinases coregulate a molecular switch in the phosphoinositide 3-kinase regulatory subunit. Cancer Cell 2002, 1:181-191.
10. Chaussade C., Cho K., Mawson C., Rewcastle G.W., Shepherd P.R. Functional differences between two classes of oncogenic mutation in the PIK3CA gene. Biochem. Biophys. Res. Commun. 2009, 381:577-581.
11. Ciraolo E., Iezzi M., Marone R., Marengo S., Curcio C., Costa C., Azzolino O., Gonella C., Rubinetto C., Wu H., et al. Phosphoinositide 3-kinase p110beta activity: key role in metabolism and mammary gland cancer but not development. Sci. Signal. 2008, 1:ra3.
12. Ciraolo E., Morello F., Hobbs R.M., Wolf F., Marone R., Iezzi M., Lu X., Mengozzi G., Altruda F., Sorba G., et al. Essential role of the p110beta subunit of phosphoinositide 3-OH kinase in male fertility. Mol. Biol. Cell 2010, 21:704-711.
13. Cuevas B.D., Lu Y., Mao M., Zhang J., LaPushin R., Siminovitch K., Mills G.B. Tyrosine phosphorylation of p85 relieves its inhibitory activity on phosphatidylinositol 3-kinase. J. Biol. Chem. 2001, 276:27455-27461.
14. Dbouk H.A., Pang H., Fiser A., Backer J.M. A biochemical mechanism for the oncogenic potential of the p110beta catalytic subunit of phosphoinositide 3-kinase. Proc. Natl. Acad. Sci. USA 2010, 107:19897-19902.
15. Denley A., Kang S., Karst U., Vogt P.K. Oncogenic signaling of class I PI3K isoforms. Oncogene 2008, 27:2561-2574.
16. Eck M.J., Shoelson S.E., Harrison S.C. Recognition of a high-affinity phosphotyrosyl peptide by the Src homology-2 domain of p56lck. Nature 1993, 362:87-91.
17. Engelman J.A., Luo J., Cantley L.C. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat. Rev. Genet. 2006, 7:606-619.
18. Folkes A.J., Ahmadi K., Alderton W.K., Alix S., Baker S.J., Box G., Chuckowree I.S., Clarke P.A., Depledge P., Eccles S.A., et al. The identification of 2-(1H-indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (GDC-0941) as a potent, selective, orally bioavailable inhibitor of class I PI3 kinase for the treatment of cancer. J. Med. Chem. 2008, 51:5522-5532.
19. Guillermet-Guibert J., Bjorklof K., Salpekar A., Gonella C., Ramadani F., Bilancio A., Meek S., Smith A.J., Okkenhaug K., Vanhaesebroeck B. The p110beta isoform of phosphoinositide 3-kinase signals downstream of G protein-coupled receptors and is functionally redundant with p110gamma. Proc. Natl. Acad. Sci. USA 2008, 105:8292-8297.
20. Herbst J.J., Andrews G., Contillo L., Lamphere L., Gardner J., Lienhard G.E., Gibbs E.M. Potent activation of phosphatidylinositol 3'-kinase by simple phosphotyrosine peptides derived from insulin receptor substrate 1 containing two YMXM motifs for binding SH2 domains. Biochemistry 1994, 33:9376-9381.
21. Hoedemaeker F.J., Siegal G., Roe S.M., Driscoll P.C., Abrahams J.P. 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, 292:763-770.
22. Huang H., Li L., Wu C., Schibli D., Colwill K., Ma S., Li C., Roy P., Ho K., Songyang Z., et al. Defining the specificity space of the human SRC homology 2 domain. Mol. Cell. Proteomics 2008, 7:768-784.
23. Hübner S., Couvillon A.D., Käs J.A., Bankaitis V.A., Vegners R., Carpenter C.L., Janmey P.A. Enhancement of phosphoinositide 3-kinase (PI 3-kinase) activity by membrane curvature and inositol-phospholipid-binding peptides. Eur. J. Biochem. 1998, 258:846-853.
24. Jackson S.P., Schoenwaelder S.M., Goncalves I., Nesbitt W.S., Yap C.L., Wright C.E., Kenche V., Anderson K.E., Dopheide S.M., Yuan Y., et al. PI 3-kinase p110beta: a new target for antithrombotic therapy. Nat. Med. 2005, 11:507-514.
25. Jaiswal B.S., Janakiraman V., Kljavin N.M., Chaudhuri S., Stern H.M., Wang W., Kan Z., Dbouk H.A., Peters B.A., Waring P., et al. Somatic mutations in p85alpha promote tumorigenesis through class IA PI3K activation. Cancer Cell 2009, 16:463-474.
26. Jia S., Liu Z., Zhang S., Liu P., Zhang L., Lee S.H., Zhang J., Signoretti S., Loda M., Roberts T.M., Zhao J.J. Essential roles of PI(3)K-p110beta in cell growth, metabolism and tumorigenesis. Nature 2008, 454:776-779.
27. Jimenez C., Jones D.R., Rodríguez-Viciana P., Gonzalez-García A., Leonardo E., Wennström S., von Kobbe C., Toran J.L., R-Borlado L., Calvo V., et al. Identification and characterization of a new oncogene derived from the regulatory subunit of phosphoinositide 3-kinase. EMBO J. 1998, 17:743-753.
28. Jücker M., Südel K., Horn S., Sickel M., Wegner W., Fiedler W., Feldman R.A. Expression of a mutated form of the p85alpha regulatory subunit of phosphatidylinositol 3-kinase in a Hodgkin's lymphoma-derived cell line (CO). Leukemia 2002, 16:894-901.
29. Kang S., Denley A., Vanhaesebroeck B., Vogt P.K. Oncogenic transformation induced by the p110beta, -gamma, and -delta isoforms of class I phosphoinositide 3-kinase. Proc. Natl. Acad. Sci. USA 2006, 103:1289-1294.
30. Klink T.A., Kleman-Leyer K.M., Kopp A., Westermeyer T.A., Lowery R.G. Evaluating PI3 kinase isoforms using Transcreener ADP assays. J. Biomol. Screen. 2008, 13:476-485.
31. Knight Z.A., Gonzalez B., Feldman M.E., Zunder E.R., Goldenberg D.D., Williams O., Loewith R., Stokoe D., Balla A., Toth B., et al. A pharmacological map of the PI3-K family defines a role for p110alpha in insulin signaling. Cell 2006, 125:733-747.
32. Knight Z.A., Feldman M.E., Balla A., Balla T., Shokat K.M. A membrane capture assay for lipid kinase activity. Nat. Protoc. 2007, 2:2459-2466.
33. Kulathu Y., Hobeika E., Turchinovich G., Reth M. The kinase Syk as an adaptor controlling sustained calcium signalling and B-cell development. EMBO J. 2008, 27:1333-1344.
34. Kurosu H., Maehama T., Okada T., Yamamoto T., Hoshino S., Fukui Y., Ui M., Hazeki O., Katada T. Heterodimeric phosphoinositide 3-kinase consisting of p85 and p110beta is synergistically activated by the betagamma subunits of G proteins and phosphotyrosyl peptide. J. Biol. Chem. 1997, 272:24252-24256.
35. Lempiäinen H., Halazonetis T.D. Emerging common themes in regulation of PIKKs and PI3Ks. EMBO J. 2009, 28:3067-3073.
36. Maier U., Babich A., Nürnberg B. Roles of non-catalytic subunits in gbetagamma-induced activation of class I phosphoinositide 3-kinase isoforms beta and gamma. J. Biol. Chem. 1999, 274:29311-29317.
37. Mandelker D., Gabelli S.B., Schmidt-Kittler O., Zhu J., Cheong I., Huang C.H., Kinzler K.W., Vogelstein B., Amzel L.M. A frequent kinase domain mutation that changes the interaction between PI3Kalpha and the membrane. Proc. Natl. Acad. Sci. USA 2009, 106:16996-17001.
38. Marqués M., Kumar A., Poveda A.M., Zuluaga S., Hernández C., Jackson S., Pasero P., Carrera A.C. Specific function of phosphoinositide 3-kinase beta in the control of DNA replication. Proc. Natl. Acad. Sci. USA 2009, 106:7525-7530.
39. Martin V., Guillermet-Guibert J., Chicanne G., Cabou C., Jandrot-Perrus M., Plantavid M., Vanhaesebroeck B., Payrastre B., Gratacap M.P. Deletion of the p110beta isoform of phosphoinositide 3-kinase in platelets reveals its central role in Akt activation and thrombus formation in vitro and in vivo. Blood 2010, 115:2008-2013.
40. Miled N., Yan Y., Hon W.C., Perisic O., Zvelebil M., Inbar Y., Schneidman-Duhovny D., Wolfson H.J., Backer J.M., Williams R.L. Mechanism of two classes of cancer mutations in the phosphoinositide 3-kinase catalytic subunit. Science 2007, 317:239-242.
41. Miller S., Tavshanjian B., Oleksy A., Perisic O., Houseman B.T., Shokat K.M., Williams R.L. Shaping development of autophagy inhibitors with the structure of the lipid kinase Vps34. Science 2010, 327:1638-1642.
42. Parsons D.W., Jones S., Zhang X., Lin J.C., Leary R.J., Angenendt P., Mankoo P., Carter H., Siu I.M., Gallia G.L., et al. An integrated genomic analysis of human glioblastoma multiforme. Science 2008, 321:1807-1812.
43. Pauptit R.A., Dennis C.A., Derbyshire D.J., Breeze A.L., Weston S.A., Rowsell S., Murshudov G.N. NMR trial models: experiences with the colicin immunity protein Im7 and the p85alpha C-terminal SH2-peptide complex. Acta Crystallogr. D Biol. Crystallogr. 2001, 57:1397-1404.
44. Pawson T., Nash P. Assembly of cell regulatory systems through protein interaction domains. Science 2003, 300:445-452.
45. Rordorf-Nikolic T., Van Horn D.J., Chen D., White M.F., Backer J.M. Regulation of phosphatidylinositol 3'-kinase by tyrosyl phosphoproteins. Full activation requires occupancy of both SH2 domains in the 85-kDa regulatory subunit. J. Biol. Chem. 1995, 270:3662-3666.
46. Schlessinger J., Lemmon M.A. SH2 and PTB domains in tyrosine kinase signaling. Sci. STKE 2003, 2003:RE12.
47. Songyang Z., Shoelson S.E., Chaudhuri M., Gish G., Pawson T., Haser W.G., King F., Roberts T., Ratnofsky S., Lechleider R.J., et al. SH2 domains recognize specific phosphopeptide sequences. Cell 1993, 72:767-778.
48. Stock D., Perisic O., Löwe J. Robotic nanolitre protein crystallisation at the MRC Laboratory of Molecular Biology. Prog. Biophys. Mol. Biol. 2005, 88:311-327.
49. Vanhaesebroeck B., Alessi D.R. The PI3K-PDK1 connection: more than just a road to PKB. Biochem. J. 2000, 346:561-576.
50. Vanhaesebroeck B., Guillermet-Guibert J., Graupera M., Bilanges B. The emerging mechanisms of isoform-specific PI3K signalling. Nat. Rev. Mol. Cell Biol. 2010, 11:329-341.
51. Vogt P.K., Gymnopoulos M., Hart J.R. PI 3-kinase and cancer: changing accents. Curr. Opin. Genet. Dev. 2009, 19:12-17.
52. Wu H., Shekar S.C., Flinn R.J., El-Sibai M., Jaiswal B.S., Sen K.I., Janakiraman V., Seshagiri S., Gerfen G.J., Girvin M.E., Backer J.M. Regulation of Class IA PI 3-kinases: C2 domain-iSH2 domain contacts inhibit p85/p110alpha and are disrupted in oncogenic p85 mutants. Proc. Natl. Acad. Sci. USA 2009, 106:20258-20263.
53. Yu J., Wjasow C., Backer J.M. Regulation of the p85/p110alpha phosphatidylinositol 3'-kinase. Distinct roles for the n-terminal and c-terminal SH2 domains. J. Biol. Chem. 1998, 273:30199-30203.
54. Zhao J.J., Liu Z., Wang L., Shin E., Loda M.F., Roberts T.M. The oncogenic properties of mutant p110alpha and p110beta phosphatidylinositol 3-kinases in human mammary epithelial cells. Proc. Natl. Acad. Sci. USA 2005, 102:18443-18448.