The nuclear phosphoinositide 3-kinase/AKT pathway: A new second messenger system

Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids

Volumn 1584, Issue 2-3, 2002, Pages 73-80

  Neri, Luca M ^a   Borgatti, Paola ^a   Capitani, Silvano ^a   Martelli, Alberto M ^b,c  

^a UNIVERSITY OF FERRARA   (Italy)

^b CNR   (Italy)

^c UNIVERSITY OF BOLOGNA   (Italy)

Author keywords

Akt; Cell differentiation; Nucleus; PI3K; Signal transduction; Transcription factor

Indexed keywords

CASPASE 9; CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN; GREEN FLUORESCENT PROTEIN; GUANINE NUCLEOTIDE BINDING PROTEIN; I KAPPA B KINASE; INOSITOL; MAMMALIAN TARGET OF RAPAMYCIN; NERVE GROWTH FACTOR; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PLATELET DERIVED GROWTH FACTOR; PROTEIN; PROTEIN BAD; PROTEIN FRAP; PROTEIN GSK 3 ALPHA; PROTEIN GSK 3 BETA; PROTEIN KINASE B; PROTEIN KINASE C; PROTEIN NUMA; PROTEIN P21; SOMATOMEDIN C; TRANSCRIPTION FACTOR; UNCLASSIFIED DRUG;

APOPTOSIS; CANCER GROWTH; CELL FUNCTION; CELL PROLIFERATION; ENZYME ACTIVITY; HUMAN; LIPID METABOLISM; MOLECULE; NONHUMAN; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; PROTEIN PHOSPHORYLATION; REVIEW; SECOND MESSENGER; SEQUENCE HOMOLOGY;

1-PHOSPHATIDYLINOSITOL 3-KINASE; ANIMALS; CELL LINE; CELL NUCLEUS; HUMANS; PROTEIN-SERINE-THREONINE KINASES; PROTO-ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS C-AKT; SECOND MESSENGER SYSTEMS; SIGNAL TRANSDUCTION;

EID: 0037057801     PISSN: 13881981     EISSN: None     Source Type: Journal    
DOI: 10.1016/S1388-1981(02)00300-1     Document Type: Review

References (73)

1. Martin T.E. Phosphoinositide lipids as signaling molecules: common themes for signal transduction, cytoskeletal regulation, and membrane trafficking. Annu. Rev. Cell Dev. Biol. 14:1998;231-264.
2. Fruman D.A., Meyers R.E., Cantley L.C. Phosphoinositide kinases. Annu. Rev. Biochem. 67:1998;481-507.
3. Leevers S.J., Vanhaesebroeck B., Waterfield M.D. Signalling through phosphoinositide 3-kinases: the lipids take centre stage. Curr. Opin. Cell Biol. 11:1999;219-225.
4. Vanhaesebroeck B., Waterfield M.D. Signaling by distinct classes of phosphoinositide 3-kinases. Exp. Cell Res. 253:1999;239-254.
5. Cantrell D.A. Phosphoinositide 3-kinase signalling pathways. J. Cell Sci. 114:2001;1439-1445.
6. Roymans R., Slegers H. Phosphatidylinositol 3-kinases in tumor progression. Eur. J. Biochem. 268:2001;487-498.
7. Brazil D.P., Hemmings D.A. Ten years of protein kinase B signalling: a hard Akt to follow. Trends Biochem. Sci. 26:2001;657-664.
8. Lawlor M.A., Alessi D.R. PKB/Akt: a key mediator of cell proliferation, survival and insulin responses? J. Cell Sci. 114:2001;2903-2910.
9. D'Santos C.S., Clarke J.H., Divecha N. Phospholipid signalling in the nucleus. Een DAG uit het leven van de inositide signalering in de nucleus Biochim. Biophys. Acta. 1436:1998;201-232.
10. Neri L.M., Capitani S., Borgatti P., Martelli A.M. Lipid signaling and cell responses at the nuclear level. Histol. Histopathol. 14:1999;321-335.
11. Martelli A.M., Capitani S., Neri L.M. The generation of lipid signaling molecules in the nucleus. Prog. Lipid Res. 38:1999;273-308.
12. Cocco L., Martelli A.M., Gilmour R.S., Rhee S.G., Manzoli F.A. Nuclear phospholipase C and signaling. Biochim. Biophys. Acta. 1530:2001;1-14.
13. Martelli A.M., Bortul R., Tabellini G., Aluigi M., Peruzzi D., Bareggi R., Narducci P., Cocco L. Re-examination of the mechanisms regulating nuclear inositol lipid metabolism. FEBS Lett. 505:2001;1-6.
14. Vanhaesebroeck B., Leevers S.J., Ahmadi K., Timms J., Katso R., Driscoll P.C., Woscholski R., Parker P.J., Waterfield M.D. Synthesis and function of 3-phosphorylated inositol lipids. Annu. Rev. Biochem. 70:2001;535-602.
15. Simpson L., Parsons R. PTEN: life as a tumor suppressor. Exp. Cell Res. 264:2001;29-41.
16. Bunney T.D., Watkins P.A.C., Beven A.F., Shaw P.J., Hernandez L.E., Lomonossoff G.P., Shanks M., Peart J., Drøbak B.K. Association of phosphatidylinositol 3-kinase with nuclear transcription sites in higher plants. Plant Cell. 12:2000;1679-1688.
17. Nicholson K.M., Anderson N.G. The protein kinase B/Akt signalling pathway in human malignancy. Cell. Signal. 14:2002;381-395.
18. O'Gorman D.M., Cotter T.G. Molecular signals in anti-apoptotic survival pathways. Leukemia. 15:2001;21-34.
19. Neri L.M., Martelli A.M., Borgatti P., Colamussi M.L., Marchisio M., Capitani S. Increase in nuclear phosphatidylinositol 3-kinase activity and phosphatidylinositol (3,4,5) trisphosphate synthesis precede PKC-ζ translocation to the nucleus of NGF-treated PC12 cells. FASEB J. 13:1999;2299-2310.
20. Tanaka K., Horiguki K., Yoshida T., Takeda M., Fujisawa H., Umeda M., Kato S., Ihara S., Nagata S., Fukui Y. Evidence that a phosphatidylinositol 3,4,5-trisphosphate-binding protein can function in nucleus. J. Biol. Chem. 274:1999;3919-3922.
21. Neri L.M., Bortul R., Tabellini G., Borgatti P., Baldini G., Celeghini C., Capitani S., Martelli A.M. Erythropoietin-induced erythroid differentiation of K562 cells is accompanied by the nuclear translocation of phosphatidylinositol 3-kinase and intranuclear generation of phosphatidylinositol (3,4,5) trisphosphate. Cell. Signal. 14:2002;21-29.
22. Gillooly D.J., Morrow I.C., Lindsay M., Gould R., Bryant N.J., Gaullier J.-M., Parton R.G., Stenmark H. Localization of phosphatidylinositol 3-phosphate in yeast and mammalian cells. EMBO J. 19:2000;4577-4588.
23. Yokogawa T., Nagata S., Nishio Y., Tsutsumi T., Ihara S., Shirai R., Morita K., Umeda M., Shirai Y., Saitoh N., Fukui Y. Evidence that 3′-phosphorylated polyphosphoinositides are generated at the nuclear surface: use of immunostaining technique with monoclonal antibodies specific for PI 3,4-P(2). FEBS Lett. 473:2000;222-226.
24. Tanaka K., Imajoh-Ohmi S., Swada T., Shirai S., Hashimoto Y., Iwasaki S., Kaibuchi K., Kanaho Y., Shirai T., Tereda Y., Kimura K., Nagata S., Fukui Y. A target of phosphatidylinositol 3,4,5-trisphosphate with a zinc finger motif similar to that of the ADP-ribosylation-factor GTPase-activating protein and two pleckstrin homology domains. Eur. J. Biochem. 245:1997;512-519.
25. Hammonds-Odie L.-P., Jackson T.R., Profit A.A., Blader I.J., Turck C.W., Prestwich G.D., Theibert A.B. Identification and cloning of centaurin-α. A novel phosphatidylinositol 3,4,5-trisphosphate-binding protein from rat brain. J. Biol. Chem. 271:1996;18859-18868.
26. 3. FEBS Lett. 405:1997;229-236.
27. Venkateswarlu K., Cullen P.J. Molecular cloning and functional characterization of a human homologue of centaurin-α Biochem. Biophys. Res. Commun. 262:1999;237-244.
28. Venkateswarlu K., Oatey P.A., Tavarè J.M., Jackson T.R., Cullen P.J. Identification of centaurin-α1 as a potential in vivo phosphatidylinositol 3,4,5-trisphosphate-binding protein that is functionally homologous to the yeast ADP-ribosylation factor (ARF) GTPase-activating protein, Gcs1. Biochem. J. 340:1999;359-363.
29. Neri L.M., Milani D., Bertolaso L., Stroscio M., Bertagnolo V., Capitani S. Nuclear translocation of phosphatidylinositol 3-kinase in rat pheochromocytoma PC12 cells after treatment with nerve growth factor. Cell. Mol. Biol. 40:1994;619-626.
30. Zini N., Ognibene A., Bavelloni A., Santi S., Sabatelli P., Baldini N., Scotlandi K., Serra M., Maraldi N.M. Cytoplasmic and nuclear localization sites of phosphatidylinositol 3-kinase in human osteosarcoma sensitive and multidrug-resistant Saos-2 cells. Histochem. Cell Biol. 106:1996;457-464.
31. Lu P.J., Hsu A.L., Wang D.S., Yan H.Y., Yin H.L., Chen C.S. Phosphoinositide 3-kinase in rat liver nuclei. Biochemistry. 37:1998;5738-5745.
32. Kim S.J. Insulin rapidly induces nuclear translocation of PI3-kinase in HepG2 cells. Biochem. Mol. Biol. Int. 46:1998;187-196.
33. Metjian A., Roll R.L., Ma A.D., Abrams C.S. Agonists cause nuclear translocation of phosphatidylinositol 3-kinase γ. A Gβγ-dependent pathway that requires the p110γ amino terminus. J. Biol. Chem. 274:1999;27943-27947.
34. Bacqueville D., Déléris P., Mendre C., Pieraggi M.-T., Chap H., Guillon G., Perret B., Breton-Douillon M. Characterization of a G protein-activated phosphoinositide 3-kinase in vascular smooth muscle cell nuclei. J. Biol. Chem. 276:2001;22170-22176.
35. Didichenko S.A., Thelen M. Phosphatidylinositol 3-kinase C2α contains a nuclear localization sequence and associates with nuclear speckles. J. Biol. Chem. 276:2001;48135-48142.
36. Sindic A., Aleksandrova A., Fields A.P., Volinia S., Banfic H. Presence and activation of nuclear phosphoinositide 3-kinase C2β during compensatory liver growth. J. Biol. Chem. 276:2001;17754-17761.
37. Martelli A.M., Cocco L., Riederer B.M., Neri L.M. The nuclear matrix: a critical appraisal. Histol. Histopathol. 11:1996;1035-1048.
38. Nickerson J. Experimental observations of a nuclear matrix. J. Cell Sci. 114:2001;463-474.
39. Lamond A.I., Earnshaw W.C. Structure and function in the nucleus. Science. 280:1998;547-553.
40. Matera A.G. Nuclear bodies: multifaceted subdomains of the interchromatin space. Trends Cell Biol. 9:1999;302-309.
41. Marchisio M., Bertagnolo V., Colamussi M.L., Capitani S., Neri L.M. Phosphatidylinositol 3-kinase in HL-60 nuclei is bound to the nuclear matrix and increases during granulocytic differentiation. Biochem. Biophys. Res. Commun. 253:1998;346-351.
42. Boronenkov I.V., Loijens J.C., Umeda M., Anderson R.A. Phosphoinositide signaling pathways in nuclei are associated with nuclear speckles containing pre-mRNA processing factors. Mol. Biol. Cell. 9:1998;3547-3560.
43. 2 assembles in a mitotically regulated particle involved in pre-mRNA splicing. J. Cell Sci. 114:2001;2501-2511.
44. Greene L.A. The importance of both early and delayed responses in the biological actions of nerve growth factors. Trends Neurosci. 7:1984;91-94.
45. Ye K., Hurt K.J., Wu F.Y., Fang M., Luo H.R., Hong J.J., Blackshaw S., Ferris C.D., Snyder S.H. Pike. A nuclear GTPase that enhances PI3kinase activity and is regulated by protein 4.1N. Cell. 103:2000;919-930.
46. Collins S. The HL-60 promyelocytic leukemia cell line: proliferation, differentiation, and cellular oncogene expression. Blood. 70:1987;1233-1244.
47. Neri L.M., Marchisio M., Colamussi M.L., Bertagnolo V. Monocytic differentiation of HL-60 cells is characterized by the nuclear translocation of phosphatidylinositol 3-kinase and of definite phosphatidylinositol-specific phospholipase C isoforms. Biochem. Biophys. Res. Commun. 259:1999;314-320.
48. Bertagnolo V., Neri L.M., Marchisio M., Mischiati C., Capitani S. Phosphoinositide 3-kinase activity is essential for all-trans-retinoic acid-induced granulocytic differentiation of HL-60 cells. Cancer Res. 59:1999;542-546.
49. Bavelloni A., Santi S., Sirri A., Riccio M., Faenza I., Zini N., Cecchi S., Ferri A., Auron P., Maraldi N.M., Marmiroli S. Phosphatidylinositol 3-kinase translocation to the nucleus is induced by interleukin 1 and prevented by mutation of interleukin 1 receptor in human osteosarcoma Saos-2 cells. J. Cell Sci. 112:1999;631-640.
50. Costantinescu S.N., Ghaffari S., Lodish H.F. The erythropoietin receptor: structure, activation and intracellular signal transduction. Trends Endocrinol. Metab. 10:1999;18-23.
51. Martelli A.M., Borgatti P., Bortul R., Manfredini M., Massari L., Capitani S., Neri L.M. Phosphatidylinositol 3-kinase translocates to the nucleus of osteoblast-like MC3T3-E1 cells in response to insulin-like growth factor I and platelet-derived growth factor but not to the proapoptotic cytokine tumor necrosis factor α J. Bone Miner. Res. 15:2000;1716-1730.
52. Mattagajasingh S.N., Huang S.-C., Hartenstein J.S., Snyder M., Marchesi V.T., Benz E.J., A nonerythroid isoform of protein 4.1R interacts with the nuclear mitotic apparatus (NuMA) protein J. Cell Biol. 145:1999;29-43.
53. Yu H., Fukami K., Watanabe Y., Ozaki C., Takenawa T. Phosphatidylinositol 4,5-bisphosphate reverses the inhibition of RNA transcription caused by histone H1. Eur. J. Biochem. 251:1998;281-287.
54. 3. J. Biol. Chem. 269:1994;32358-32367.
55. Calcerrada M.C., Miguel B.M., Martin L., Catalan R.R., Martinez M. Involvement of phosphatydilinositol 3-kinase in nuclear translocation of PKCζ induced by C2-ceramide in rat hepatocytes. FEBS Lett. 514:2002;361-365.
56. Wooten M.W., Zhou G., Wooten M.C., Seibenhener M.L. Transport of protein kinase C isoforms to the nucleus of PC12 cells by nerve growth factor: association of atypical zeta-PKC with the nuclear matrix. J. Neurosci. Res. 49:1997;393-403.
57. Ginisty H., Sicard H., Roger B., Bouvet P. Structure and functions of nucleolin. J. Cell Sci. 112:1999;761-772.
58. Zhou G., Seibenhener M.L., Wooten M.W. Nucleolin is a protein kinase C-ζ substrate. Connection between cell surface signaling and nucleus in PC12 cells. J. Biol. Chem. 272:1997;31130-31137.
59. Municio M.M., Lozano J., Sanchez P., Moscat J., Diaz-Meco M.T. Identification of heterogeneous ribonucleoprotein A1 as a novel substrate for protein kinase C ζ J. Biol. Chem. 270:1995;15884-15891.
60. Brownawell A.M., Kops G.J.P.L., Macara I.G., Burgering B.M.T. Inhibition of nuclear import by protein kinase B (Akt) regulates the subcellular distribution and activity of the forkhead transcription factor AFX. Mol. Cell. Biol. 21:2001;3543-3546.
61. Andjelković M., Alessi D.R., Meier R., Fernandez A., Lamb N.J.C., Frech M., Cron P., Cohen P., Lucocq J.M., Hemmings B.A. Role of translocation in the activation and function of protein kinase B. J. Biol. Chem. 272:1997;31515-31524.
62. Meier R., Alessi D.R., Cron P., Andjelković M., Hemmings B.A. Mitogenic activation, phosphorylation, and nuclear translocation of protein kinase Bβ J. Biol. Chem. 272:1997;30491-30497.
63. Astoul E., Watton S., Cantrell D. The dynamics of protein kinase B regulation during B cell antigen receptor engagement. J. Cell Biol. 145:1999;1511-1520.
64. Ouyang Y.-B., Zhang X.-H., He Q.-P., Wang G.-X., Siesjo B.K., Hu B.-R. Differential phosphorylation at Ser473 and Thr308 of Akt-1 in rat brain following hypoglycemic coma. Brain Res. 876:2000;191-195.
65. Borgatti P., Martelli A.M., Bellacosa A., Casto R., Massari L., Capitani S., Neri L.M. Translocation of Akt/PKB to the nucleus of osteoblast-like MC3T3-E1 cells exposed to proliferative growth factors. FEBS Lett. 477:2000;27-32.
66. Salinas M., López-Valdaliso R., Martin D., Alvarez A., Cuadrado A. Inhibition of Akt1 by C2-ceramide involves activation of ceramide-activated protein phosphatase in PC12 cells. Mol. Cell. Neurosci. 15:2000;156-169.
67. Rena G., Guo S., Cichy S.C., Unterman T.G., Cohen P. Phosphorylation of the transcription factor forkhead family member FKHR by protein kinase B. J. Biol. Chem. 274:1999;17179-17183.
68. Vandromme M., Rocha A., Meier R., Carnac G., Besser D., Lemmings B.A., Fernandez A., Lamb N.J.C. Protein kinase B β/Akt2 plays a specific role in muscle differentiation. J. Biol. Chem. 276:2001;8173-8179.
69. Pekarsky Y., Hallas C., Croce C.M. Molecular basis of mature T-cell leukemia. JAMA. 286:2001;2308-2314.
70. Pekarsky Y., Koval A., Hallas C., Bichi R., Tresini M., Malstrom S., Russo G., Tsichlis P., Croce C.M. Tcl1 enhances Akt kinase activity and mediates its nuclear translocation. Proc. Natl. Acad. Sci. U. S. A. 97:2000;3028-3033.
71. Lachyankar M.B., Sultana N., Schonhoff C.M., Mitra P., Poluha W., Lambert S., Quesenberry P.J., Litofsky N.S., Recht L.D., Nabi R., Miller S.J., Ohta S., Neel B.G., Ross A.H. A role for PTEN in neuronal differentiation. J. Neurosci. 20:2000;1404-1413.
72. McCright B., Rivers A.M., Audlin S., Virshup D.M. The B56 family of protein phosphatase 2A (PP2A) regulatory subunits encodes differentiation-induced phosphoproteins that target PP2A to both nucleus and cytoplasm. J. Biol. Chem. 271:1996;22081-22089.
73. Li H., Zhao L.L., Funder J.W., Liu J.P. Protein phosphatase 2A inhibits nuclear telomerase activity in human breast cancer cells. J. Biol. Chem. 272:1997;16729-16732.