PI3K/Akt and apoptosis: size matters

被引:1029
作者
Franke, TF [1 ]
Hornik, CP [1 ]
Segev, L [1 ]
Shostak, GA [1 ]
Sugimoto, C [1 ]
机构
[1] Columbia Univ Coll Phys & Surg, Dept Pharmacol, New York, NY 10032 USA
关键词
Akt; PI3K; PTEN; PDK2; apoptosis; genetic models;
D O I
10.1038/sj.onc.1207115
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Recent research has examined Akt and Akt-related serine-threonine kinases in signaling cascades that regulate cell survival and are important in the pathogenesis of degenerative diseases and in cancer. W e seek to recapitulate the research that has helped to de. ne the current understanding of the role of the Akt pathway under normal and pathologic conditions, also in view of genetic models of Akt function. In particular, we will evaluate the mechanisms of Akt regulation and the role of Akt substrates in Akt-dependent biologic responses in the decisions of cell death and cell survival. Here, we hope to establish the mechanisms of apoptosis suppression by Akt kinase as a framework for a more general understanding of growth factor-dependent regulation of cell survival.
引用
收藏
页码:8983 / 8998
页数:16
相关论文
共 267 条
[1]  
AHMED NN, 1993, ONCOGENE, V8, P1957
[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]   Mechanism of activation and function of protein kinase B [J].
Alessi, DR ;
Cohen, P .
CURRENT OPINION IN GENETICS & DEVELOPMENT, 1998, 8 (01) :55-62
[4]   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
[5]   The inositol phosphatase SHIP inhibits Akt/PKB activation in B cells [J].
Aman, MJ ;
Lamkin, TD ;
Okada, H ;
Kurosaki, T ;
Ravichandran, KS .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (51) :33922-33928
[6]   Activation and phosphorylation of a pleckstrin homology domain containing protein kinase (RAC-PK/PKB) promoted by serum and protein phosphatase inhibitors [J].
Andjelkovic, M ;
Jakubowicz, T ;
Cron, P ;
Ming, XF ;
Han, JW ;
Hemmings, BA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (12) :5699-5704
[7]   The Akt kinase:: Molecular determinants of oncogenicity [J].
Aoki, M ;
Batista, O ;
Bellacosa, A ;
Tsichlis, P ;
Vogt, PK .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (25) :14950-14955
[8]   A role of the kinase mTOR in cellular transformation induced by the oncoproteins P3k and Akt [J].
Aoki, M ;
Blazek, E ;
Vogt, PK .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (01) :136-141
[9]   Phosphorylation of HDM2 by Akt [J].
Ashcroft, M ;
Ludwig, RL ;
Woods, DB ;
Copeland, TD ;
Weber, HO ;
MacRae, EJ ;
Vousden, KH .
ONCOGENE, 2002, 21 (13) :1955-1962
[10]   The dynamics of protein kinase B regulation during B cell antigen receptor engagement [J].
Astoul, E ;
Watton, S ;
Cantrell, D .
JOURNAL OF CELL BIOLOGY, 1999, 145 (07) :1511-1520