Abstract
Cells of multicellular organisms require extracellular signals to survive. Numerous studies have implicated a variety of intracellular signaling pathways, including PI-3 kinase/Akt, Ras/mitogen-activated protein kinase, and Jak/signal transducers and activators of transcription, as effectors of these extracellular trophic factors. Binding of growth factors to their respective receptors results in the activation of individual and combined pathways resulting in pleiotropic effects on cellular biochemistry. Over the past decade, investigation of these pathways has provided insight into the mechanism of cell survival and apoptosis itself. The results of these studies are providing new clues for therapeutic intervention in human disease. In this review, we focus on advances in our current understanding of the receptor signaling pathways that regulate apoptosis. Implications for the pharmacological manipulation of apoptosis in the treatment of cancer are also discussed.
Footnotes
-
Due to space limitations, citation of all relevant primary literature was not possible, and a complete list of references may be requested by contacting C.B.T.
- Abbreviations:
- PI3K
- PI-3 kinase
- Akt
- c-Akt
- BH
- Bcl-2 homology
- DD
- death domain
- FasL
- Fas ligand
- MAPK
- mitogen-activated protein kinase
- PTEN
- phosphatase and tensin homolog deleted from chromosome 10
- PI
- phosphatidylinositol
- PIP
- PI-3′ phosphate
- PH
- pleckstrin homology
- STAT
- signal transducers and activators of transcription
- tBID
- truncated BID
- TNF
- tumor necrosis factor
- TNFR
- TNF receptor
- VDAC
- voltage-dependent anion channel
- S136
- serine 136
- Rsk
- ribosomal S6 kinase
- NF-κB
- nuclear factor κB
- IL
- interleukin
- Received January 11, 2001.
- Accepted April 30, 2001.
- The American Society for Pharmacology and Experimental Therapeutics
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|