Bifurcation of lipid and protein kinase signals of PI3Kγ to the protein kinases PKB and MAPK

Science

Volumn 282, Issue 5387, 1998, Pages 293-296

  Bondeva, Tzvetanka ^a   Pirola, Luciano ^b   Bulgarelli Leva, Ginette ^b   Rubio, Ignacio ^a   Wetzker, Reinhard ^a   Wymann, Matthias P ^b  

^a FRIEDRICH SCHILLER UNIVERSITY JENA   (Germany)

^b UNIVERSITY OF FRIBOURG   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

LIPID; MITOGEN ACTIVATED PROTEIN KINASE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE;

ARTICLE; CATALYSIS; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME ANALYSIS; ENZYME INACTIVATION; ENZYME SUBSTRATE; HUMAN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION;

1-PHOSPHATIDYLINOSITOL 3-KINASE; AMINO ACID SEQUENCE; ANDROSTADIENES; ANIMALS; BINDING SITES; CA(2+)-CALMODULIN DEPENDENT PROTEIN KINASE; CELL MEMBRANE; CERCOPITHECUS AETHIOPS; COS CELLS; ENZYME ACTIVATION; LYSOPHOSPHOLIPIDS; MAP KINASE KINASE 1; MITOGEN-ACTIVATED PROTEIN KINASE 1; MITOGEN-ACTIVATED PROTEIN KINASE KINASES; MOLECULAR SEQUENCE DATA; MYELIN BASIC PROTEINS; PHOSPHATIDYLINOSITOL PHOSPHATES; PHOSPHORYLATION; PROTEIN-SERINE-THREONINE KINASES; PROTEIN-TYROSINE KINASES; PROTO-ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS C-AKT; RECOMBINANT PROTEINS; SIGNAL TRANSDUCTION; TRANSFECTION;

EID: 0032500730     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.282.5387.293     Document Type: Article

References (23)

1. B. Vanhaesebroeck, S. J. Leevers, G. Panayotou, M. D. Waterfield, Trends Biochem. Sci. 22, 267 (1997); A. Toker, and L. C. Cantley, Nature 387, 673 (1997).
2. B. Vanhaesebroeck, S. J. Leevers, G. Panayotou, M. D. Waterfield, Trends Biochem. Sci. 22, 267 (1997); A. Toker, and L. C. Cantley, Nature 387, 673 (1997).
3. T. F. Franke, D. R. Kaplan, L. C. Cantley, A. Toker, Science 275, 665 (1997); A. Klippel, W. M. Kavanaugh, D. Pot, L. T. Williams, Mol. Cell. Biol. 17, 338 (1997).
4. T. F. Franke, D. R. Kaplan, L. C. Cantley, A. Toker, Science 275, 665 (1997); A. Klippel, W. M. Kavanaugh, D. Pot, L. T. Williams, Mol. Cell. Biol. 17, 338 (1997).
5. D. R. Alessi et al., Curr. Biol. 7, 261 (1997); D. Stokoe et al., Science 277, 567 (1997); L. Stephens et al., ibid. 279, 710 (1998).
6. D. R. Alessi et al., Curr. Biol. 7, 261 (1997); D. Stokoe et al., Science 277, 567 (1997); L. Stephens et al., ibid. 279, 710 (1998).
7. D. R. Alessi et al., Curr. Biol. 7, 261 (1997); D. Stokoe et al., Science 277, 567 (1997); L. Stephens et al., ibid. 279, 710 (1998).
8. C. L. Carpenter et al., Mol. Cell. Biol. 13, 1657 (1993); R. Dhand et al., EMBO J. 13, 522 (1994).
9. C. L. Carpenter et al., Mol. Cell. Biol. 13, 1657 (1993); R. Dhand et al., EMBO J. 13, 522 (1994).
10. S. Stoyanova et al., Biochem. J. 324, 489 (1997).
11. A. Arcaro and M. P. Wymann, ibid. 296, 297 (1993).
12. M. P. Wymann et al., Mol. Cell. Biol. 16, 1722 (1996).
13. B. Stoyanov et al., Science 269, 690 (1995); L. R. Stephens et al., Cell 89, 105 (1997).
14. B. Stoyanov et al., Science 269, 690 (1995); L. R. Stephens et al., Cell 89, 105 (1997).
15. L. Pirola, G. Bulgarelli-Leva, M. Zvelebil, M. D. Waterfield, M. P. Wymann, in preparation.
16. L. Pirola and M. P. Wymann, unpublished data.
17. M. Lopez-Ilasaca, P. Crespo, P. C. Pellici, J. S. Gutkind, R. Wetzker, Science 275, 394 (1997).
18. P. Rodriguez-Viciana et al., EMBO J. 15, 2442 (1996).
19. I. Rubio et al., Biochem. J. 326, 891 (1997).
20. 227 → Glu Ras-binding mutant of PI3Kα by Rodriguez-Viciana et al. (12), reduced Ras binding by >80% (T. Bondeva, unpublished data).
21. PI3Kγ hybrids were generated by the introduction of synthetic oligonucleotides to replace PI3Kγ coding sequences between Avr I and Kpn I restriction sites (Fig. 1A). Manipulated regions were sequenced, subcloned into a cytomegalovirus promoter-driven expression vector (pSTC-tkGST) (7), and transfected by the calcium phosphate method into 293 cells. In vitro kinase assays with immobilized proteins were done as described in (6).
22. 4]. Myelin basic protein was the substrate for Erk2 and MEK1; for PKB assays, crosstide peptide was used [R. Meier, D. R. Alessi, P. Cron, M. Andjelkovic, B. A. Hemmings, J. Biol. Chem. 272, 30491 (1997)].
23. We thank K.-L. Guan for MEK, R. Marais for Raf, T. Franke for PKB expression plasmids, S. Gutkind for plasmids described in (11), B. Hemmings and R. Meier for help with the PKB assay and crosstide peptide, and A. Schneider tor criticism. Supported by Swiss National Science Foundation grant 3100-50506.97 (to M.P.W.).