REVIEW: Phosphatidylinositol-3 Kinase Dependent Pathways: the Role in
Control of Cell Growth, Survival, and Malignant Transformation
M. A. Krasilnikov
Institute of Carcinogenesis, Blokhin Cancer Research Center, Russian
Academy of Medical Sciences, Kashirskoe Shosse 24, Moscow, 115478
Russia; fax: (095) 324-1205; E-mail:
mkras@mail.cnt.ru
Received September 17, 1999
Phosphatidylinositol-3 kinase (PI3K) is one of the most important
regulatory proteins that is involved in different signaling pathways
and controlling of key functions of the cell. The double-enzymatic
activity of PI3K (lipid kinase and protein kinase) as well as the
ability of this enzyme to activate a number of signal proteins
including some oncoproteins determines its fundamental significance in
regulation of cell functions such as growth and survival, aging, and
malignant transformation. Among the main effectors of PI3K are the
mitogen-transducing signal proteins (protein kinase C,
phosphoinositide-dependent kinases, small G-proteins, MAP (mitogen
activated protein) kinases), which are activated either via their
interaction with lipid products of PI3K or through PI3K-dependent
phosphorylation of proteins. The anti-apoptotic effect of PI3K is
realized by activation of proteins from another signaling
pathway--protein kinase B (PKB) and/or PKB-dependent enzymes (GSK-3,
ILK). PI3K plays a critical role in malignant transformation. PI3K
itself possesses oncogenic activity and also forms complexes with some
viral or cellular oncoproteins (src, ras, rac, alb, T-antigen), whose
transforming activities are realized only in presence of PI3K. The
transforming effect of PI3K is supposed to occur on the basis of
complex alterations in cellular signaling pathways: appearance of
constitutively generated PI3K-dependent mitogen signal and activation
of some protooncogenes (src, ras, rac, etc.),
PI3K/PKB-pathway stimulation resulting in delay of apoptosis and
increase of cell survival, and actin cytoskeleton reorganization.
KEY WORDS: phosphatidylinositol-3 kinase, phosphoinositides, MAP
kinases, protein kinase B, proliferation, apoptosis, oncogenic
transformation, aging