The emerging mechanisms of isoform-specific PI3K signalling

被引：1432
作者：
Vanhaesebroeck, Bart [1 ]
Guillermet-Guibert, Julie [1 ]
Graupera, Mariona [1 ]
Bilanges, Benoit [1 ]
机构：
[1] Queen Mary Univ London, Ctr Cell Signalling, Inst Canc, London EC1M 6BQ, England
来源：
NATURE REVIEWS MOLECULAR CELL BIOLOGY | 2010年 / 11卷 / 05期
基金：
英国医学研究理事会;
关键词：
II PHOSPHOINOSITIDE 3-KINASE; CANCER-SPECIFIC MUTATIONS; GROWTH-FACTOR RECEPTOR; LIPID KINASE-ACTIVITY; PHOSPHATIDYLINOSITOL; 3-KINASE; DISTINCT ROLES; CELL-MIGRATION; CAENORHABDITIS-ELEGANS; PHAGOSOME MATURATION; REGULATES AUTOPHAGY;
D O I：
10.1038/nrm2882
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
Phosphoinositide 3-kinases (PI3Ks) function early in intracellular signal transduction pathways and affect many biological functions. A further level of complexity derives from the existence of eight PI3K isoforms, which are divided into class I, class II and class III PI3Ks. PI3K signalling has been implicated in metabolic control, immunity, angiogenesis and cardiovascular homeostasis, and is one of the most frequently deregulated pathways in cancer. PI3K inhibitors have recently entered clinical trials in oncology. A better understanding of how the different PI3K isoforms are regulated and control signalling could uncover their roles in pathology and reveal in which disease contexts their blockade could be most beneficial.
引用
收藏
页码：329 / 341
页数：13
相关论文
共 175 条
[1]   Structural comparisons of class I phosphoinositide 3-kinases [J].
Amzel, L. Mario ;
Huang, Chuan-Hsiang ;
Mandelker, Diana ;
Lengauer, Christoph ;
Gabelli, Sandra B. ;
Vogelstein, Bert .
NATURE REVIEWS CANCER, 2008, 8 (09) :665-669
[2]   CD18-dependent activation of the neutrophil NADPH oxidase during phagocytosis of Escherichia coli or Staphylococcus aureus is regulated by class III but not class I or II PI3Ks [J].
Anderson, Karen E. ;
Boyle, Keith B. ;
Davidson, Keith ;
Chessa, Tamara A. M. ;
Kulkarni, Suhasini ;
Jarvis, Gavin E. ;
Sindrilaru, Anca ;
Scharffetter-Kochanek, Karin ;
Rausch, Oliver ;
Stephens, Len R. ;
Hawkins, Phillip T. .
BLOOD, 2008, 112 (13) :5202-5211
[3]   Class II phosphoinositide 3-kinases are downstream targets of activated polypeptide growth factor receptors [J].
Arcaro, A ;
Zvelebil, MJ ;
Wallasch, C ;
Ullrich, A ;
Waterfield, MD ;
Domin, J .
MOLECULAR AND CELLULAR BIOLOGY, 2000, 20 (11) :3817-3830
[4]   Human phosphoinositide 3-kinase C2β, the role of calcium and the C2 domain in enzyme activity [J].
Arcaro, A ;
Volinia, S ;
Zvelebil, MJ ;
Stein, R ;
Watton, SJ ;
Layton, MJ ;
Gout, I ;
Ahmadi, K ;
Downward, J ;
Waterfield, MD .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (49) :33082-33090
[5]   Genome-wide RNAi analysis of Caenorhabditis elegans fat regulatory genes [J].
Ashrafi, K ;
Chang, FY ;
Watts, JL ;
Fraser, AG ;
Kamath, RS ;
Ahringer, J ;
Ruvkun, G .
NATURE, 2003, 421 (6920) :268-272
[6]   Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum [J].
Axe, Elizabeth L. ;
Walker, Simon A. ;
Manifava, Maria ;
Chandra, Priya ;
Roderick, H. Llewelyn ;
Habermann, Anja ;
Griffiths, Gareth ;
Ktistakis, Nicholas T. .
JOURNAL OF CELL BIOLOGY, 2008, 182 (04) :685-701
[7]   Substrate specificity:: PI(3)Kγ has it both ways [J].
Backer, JM .
NATURE CELL BIOLOGY, 2005, 7 (08) :773-774
[8]   The regulation and function of Class III PI3Ks: novel roles for Vps34 [J].
Backer, Jonathan M. .
BIOCHEMICAL JOURNAL, 2008, 410 (01) :1-17
[9]   Gαq binds to p110α/p85α phosphoinositide 3-kinase and displaces Ras [J].
Ballou, LM ;
Chattopadhyay, M ;
Li, Y ;
Scarlata, S ;
Lin, RZ .
BIOCHEMICAL JOURNAL, 2006, 394 :557-562
[10]   Epidermal growth factor stimulates translocation of the class II phosphoinositide 3-kinase PI3K-C2β to the nucleus [J].
Banfic, Hrvoje ;
Visnjic, Dora ;
Mise, Nikica ;
Balakrishnan, Sanjeevi ;
Deplano, Simona ;
Korchev, Yuri E. ;
Domin, Jan .
BIOCHEMICAL JOURNAL, 2009, 422 :53-60
12345678910