HCV in chimps - an effect previously noted by other groups...

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an effect previously noted by other groups ( 14, 15 ). These results suggest that the PtdIns(3,4,5)P 3 signal can be transduced by the actions of a PtdIns(3,4,5)P 3 - activated protein kinase; thus, the regulation of this pathway is analogous to that of other sig - naling systems that respond to small mole - cule signals (adenosine 3 9 ,5 9 - monophos - phate–dependent protein kinase, protein ki - nase C, and Ca 2 1 /calmodulin - dependent protein kinases). In the PtdIns(3,4,5)P 3 pathway, the lipid signal controls PKB ac - tivity in two distinct but cooperative ways, which is reminiscent of the role of adeno - sine monophosphate (AMP) to allosterical - ly activate the AMP - activated protein ki - nase, and also to activate the kinase that phosphorylates the AMP - activated protein ( 24 ). This may ensure tight regulation of PKB at the correct membrane localization, and it will be interesting to see whether this dual regulatory principle will apply to other targets in the PI3K signaling pathway. Note added in proof : A PtdIns(3,4,5)P 3 - dependent protein kinase has been purified ( 25 ) that may be related to the upstream kinase described here. REFERENCES AND NOTES ___________________________ 1. S. P. Staal, Proc. Natl. Acad. Sci. U.S.A. 84 , 5034 (1987). 2. A. Bellacosa et al ., Oncogene 8 , 745 (1993). 3. N. N. Ahmed et al ., ibid. , p. 1957. 4. A. D. Kohn, F. Takeuchi, R. A. Roth, J. Biol. Chem. 271 , 21920 (1996). 5. M. A. Lemmon, K. M. Ferguson, J. Schlessinger, Cell 85 , 621 (1996). 6. B. M. T. Burgering and P. J. Coffer, Nature 376 , 599 (1995). 7. T. F. Franke et al ., Cell 81 , 727 (1995). 8. A. D. Kohn, K. S. Kovacina, R. A. Roth, EMBO J. 14 , 4288 (1995). 9. A. Klippel et al ., Mol. Cell. Biol. 16 , 4117 (1996); S. A. Didichenko, B. Tilton, B. A. Hemmings, K. Ballmer- Hofer, M. Thelen, Curr. Biol. 6 , 1271 (1996). 10. D. A. E. Cross, D. R. Alessi, P. Cohen, M. Andjelk- ovich, B. A. Hemmings, Nature 378 , 785 (1995). 11. T. F. Franke, D. R. Kaplan, L. C. Cantley, Cell 88 , 435 (1997). 12. D. R. Alessi et al ., EMBO J. 15 , 6541 (1996). 13. S. R. James et al ., Biochem. J. 315 , 709 (1996). 14. A. Klippel, W. M. Kavanaugh, D. Pot, L. T. Williams, Mol. Cell. Biol. 17 , 338 (1997). 15. T. F. Franke, D. R. Kaplan, L. C. Cantley, A. Toker, Science 275 , 665 (1997). 16. PSG5(HA)PKB was obtained from B. Burgering (Utre- cht University, Utrecht, The Netherlands). The cDNA encodingPKBwassubclonedintopBluescript,andphos- phorylation site and PH domain mutants were obtained with a strategy based on the polymerase chain reaction [with the use of Pfu DNA polymerase (Stratagene) and low cycle numbers]. The D PH-PKB mutant lacks the first 125 amino acids. All mutations were checked by sequencing. The appropriate cDNAs were then sub- cloned into a mammalian expression vector [pCMV3(EE)] and a baculovirus transfer vector [pAcoG1(EE)] encoding NH 2 -terminal EEEEFMPME (Glu-Glu) tags ( 25 ) (E, Glu; F, Phe; M, Met; P, Pro). 17. D. Stokoe, unpublished data.
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This note was uploaded on 07/12/2011 for the course BIO 620 taught by Professor Hardy during the Spring '11 term at University of Florida.

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HCV in chimps - an effect previously noted by other groups...

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