Forkhead transcription factors: new insights into protein kinase B (c-akt) signaling

被引:248
作者
Kops, GJPL
Burgering, BMT
机构
[1] Univ Utrecht, Physiol Chem Lab, NL-3584 CG Utrecht, Netherlands
[2] Univ Utrecht, Ctr Biomed Genet, NL-3584 CG Utrecht, Netherlands
来源
JOURNAL OF MOLECULAR MEDICINE-JMM | 1999年 / 77卷 / 09期
关键词
proto-oncogene; protein kinase B; transcription; forkheads; tumor suppression;
D O I
10.1007/s001099900050
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The proto-oncogene protein kinase B (PKB), also known as c-Akt, is a central player in a signaling pathway of which many components have been linked to tumorigenesis, Active forms of PKB as well as of its upstream activator phosphatidylinasitol 3-kinase (PI3K) have been found to be responsible for the transforming activities of certain viruses, and the negative regulator of this pathway, PTEN, is a tumor suppressor. The identification of particular downstream targets of PKB has provided us with new insights into the possible mechanism of PI3K/PKB-mediated tumorigenicity. Recently a subfamily of Forkhead transcription factors was identified as additional targets for PI3K/PKB signaling. This review discusses the studies that have led to this conclusion and the possible implications of this finding for our understanding of how PI3K/PKB activity could lead to oncogenesis.
引用
收藏
页码:656 / 665
页数:10
相关论文
共 94 条
[1]   Assessment of the roles of mitogen-activated protein kinase, phosphatidylinositol 3-kinase, protein kinase B, and protein kinase C in insulin inhibition of cAMP-induced phosphoenolpyruvate carboxykinase gene transcription [J].
Agati, JM ;
Yeagley, D ;
Quinn, PG .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (30) :18751-18759
[2]   Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase B alpha [J].
Alessi, DR ;
James, SR ;
Downes, CP ;
Holmes, AB ;
Gaffney, PRJ ;
Reese, CB ;
Cohen, P .
CURRENT BIOLOGY, 1997, 7 (04) :261-269
[3]   Molecular basis for the substrate specificity of protein kinase B; Comparison with MAPKAP kinase-1 and p70 S6 kinase [J].
Alessi, DR ;
Caudwell, FB ;
Andjelkovic, M ;
Hemmings, BA ;
Cohen, P .
FEBS LETTERS, 1996, 399 (03) :333-338
[4]   Mechanism of activation of protein kinase B by insulin and IGF-1 [J].
Alessi, DR ;
Andjelkovic, M ;
Caudwell, B ;
Cron, P ;
Morrice, N ;
Cohen, P ;
Hemmings, BA .
EMBO JOURNAL, 1996, 15 (23) :6541-6551
[5]   Cloning and characterization of three human forkhead genes that comprise an FKHR-like gene subfamily [J].
Anderson, MJ ;
Viars, CS ;
Czekay, S ;
Cavenee, WK ;
Arden, KC .
GENOMICS, 1998, 47 (02) :187-199
[6]   PDK1 acquires PDK2 activity in the presence of a synthetic peptide derived from the carboxyl terminus of PRK2 [J].
Balendran, A ;
Casamayor, A ;
Deak, M ;
Paterson, A ;
Gaffney, P ;
Currie, R ;
Downes, CP ;
Alessi, DR .
CURRENT BIOLOGY, 1999, 9 (08) :393-404
[7]   MOLECULAR ALTERATIONS OF THE AKT2 ONCOGENE IN OVARIAN AND BREAST CARCINOMAS [J].
BELLACOSA, A ;
DEFEO, D ;
GODWIN, AK ;
BELL, DW ;
CHENG, JQ ;
ALTOMARE, DA ;
WAN, MH ;
DUBEAU, L ;
SCAMBIA, G ;
MASCIULLO, V ;
FERRANDINA, G ;
PANICI, PB ;
MANCUSO, S ;
NERI, G ;
TESTA, JR .
INTERNATIONAL JOURNAL OF CANCER, 1995, 64 (04) :280-285
[8]   A RETROVIRAL ONCOGENE, AKT, ENCODING A SERINE-THREONINE KINASE CONTAINING AN SH2-LIKE REGION [J].
BELLACOSA, A ;
TESTA, JR ;
STAAL, SP ;
TSICHLIS, PN .
SCIENCE, 1991, 254 (5029) :274-277
[9]   Protein kinase B/Akt-mediated phosphorylation promotes nuclear exclusion of the winged helix transcription factor FKHR1 [J].
Biggs, WH ;
Meisenhelder, J ;
Hunter, T ;
Cavenee, WK ;
Arden, KC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (13) :7421-7426
[10]   Cloning and characterization of AFX, the gene that fuses to MLL in acute leukemias with a t(X;11)(q13;q23) [J].
Borkhardt, A ;
Repp, R ;
Haas, OA ;
Leis, T ;
Harbott, J ;
Kreuder, J ;
Hammermann, J ;
Henn, T ;
Lampert, F .
ONCOGENE, 1997, 14 (02) :195-202