Christos Tsatsanis, University of Crete, Crete, Greece
Alexandros Zafiropoulos, University of Crete, Crete, Greece
Demetrios A Spandidos, University of Crete, Crete, Greece
Published online: July 2007
DOI: 10.1002/9780470015902.a0006051.pub2
Oncogenesis involves the generation and transmission of signals that result in deregulation of cell proliferation, inhibition of apoptosis and morphological changes. Transmembrane or cytoplasmic tyrosine and serine/threonine kinases participate both directly and indirectly in cell transformation and tumorigenesis.
Keywords: tyrosine kinases; receptor kinases; serine/threonine kinases; cell cycle; apoptosis
|
Figure 1. Receptor tyrosine kinases mediate extracellular growth signals that trigger a cascade of phosphorylation events in the cytoplasm, leading to the activation of gene transcription. RPTK: receptor protein tyrosine kinase; PI3K: phospho-inositol-3-kinase; Akt: serine threonine kinase cloned from the AKT8 retrovirus; Bad: Bcl-2-related protein; Ik: IB kinase ; NIK: NfB activating-interleukin1 receptor-induced kinase; IB: inhibitor of NF B; RelA: subunit of Nf B, p50 nuclear factor B subunit; NFB: nuclear factor B, TPL-2 tumour progression locus 2; SEK: stress-induced serine threonine kinase; JNK: c-jun kinase; c-jun: component of AP1 complex; c-fos: component of AP1 complex; ERK1/2: extracellular signal regulated kinase 1 and 2; MEK1, MEKK: kinase phosphorylating MEKs; Raf1: MSV retrovirus-induced serine threonine kinase; Src: simian retrovirus induced tyrosine kinase; Abl: Abelson murine leukaemia virus-induced tyrosine kinase; SOS: GTP/GDP-exchange factor; Grb2: GTP/GDP exchange factor; Ras: transforming gene of Harvey and Kirsten sarcoma viruses; Ap1: transcription factor complex.
|
|
Figure 2. Mechanisms of apoptosis induced by death receptors or cellular stress, which are potentially inhibited by oncogenic kinases. Fas: CD95, APO1 death receptor; TNFR1: tumour necrosis factor receptor 1; FADD: Fas associated death domain; TRADD: TNF receptor associated death domain protein; TRAF2: TNF receptor associated factor 2; p38MAPK: 38 kDa mitogen-activated protein kinase; Apaf-1: apoptosis associated factor 1; CytoC: cytochrome c; IAP: inhibitor of apoptosis.
|
| References | |
| Bader AG, Kang S, Zhao L and Vogt PK (2005) Oncogenic PI3 K deregulates transcription and translation . Nature Reviews Cancer 5: 921–929. | |
| Blume-Jensen P and Hunter T (2001) Oncogenic kinase signalling. Nature 411: 355–365. | |
| Fesik SW (2005) Promoting apoptosis as a strategy for cancer drug discovery. Nature Reviews Cancer 5: 876–885. | |
| Goldman JM and Melo JV (2003) Chronic myeloid leukemia–advances in biology and new approaches to treatment. The New England Journal of Medicine 349: 1451–1464. | |
| Hanahan D and Weinberg RA (2000) The hallmarks of cancer. Cell 100: 57–70. | |
| Huang Y, Lu M and Wu H (2004) Antagonizing XIAP-mediated caspase-3 inhibition. Achilles’ heel of cancers?. Cancer Cell 5: 1–2. | |
| Klein S, McCormick F and Levitzki A (2005) Killing time for cancer cells. Nature Reviews Cancer 5: 573–580. | |
| Levine AJ, Feng Z, Mak TW, You H and Jin S (2006) Coordination and communication between the p53 and IGF-1-AKT-TOR signal transduction pathways. Genes & Development 20: 267–275. | |
| Massague J (2004) G1 cell-cycle control and cancer. Nature 432: 298–306. | |
| McLean GW, Carragher NO, Avizienyte E et al. (2005) The role of focal-adhesion kinase in cancer – a new therapeutic opportunity. Nature Reviews Cancer 5: 505–515. | |
| Meuwissen R and Berns A (2005) Mouse models for human lung cancer. Genes & Development 19: 643–664. | |
| Sabatini DM (2006) mTOR and cancer: insights into a complex relationship. Nature Reviews Cancer 6: 729–734. | |
| ePath Tsatsanis C (2006) Tpl2/Cot kinase. AfCS-Nature Molecule Pages, doi:10.1038/mp.a000092.01, http://www.signaling-gateway.org/molecule/query?afcsid=A000092 | |
| Tsatsanis C and Spandidos DA (2000) The role of oncogenic kinases in human cancer. International Journal of Molecular Medicine 5: 583–590. | |
| Zachos G and Spandidos DA (1997) Expression of ras proto-oncogenes: regulation and implications in the development of human tumors. Critical Reviews in Oncology/Hematology 26: 65–75. | |
| Further Reading | |
| other Ferrell JE (2000) Regulatory Cascades: Function and Properties. Encyclopedia of Life Sciences. London: Nature Publishing Group. http://www.els.net. | |
| other Heldin C-H (2000) Signal transduction: overview. Encyclopedia of Life Sciences. London: Nature Publishing Group. http://www.els.net. | |
| Hunter T (2000) Signaling: 2000 and beyond. Cell 100: 113–127. | |
| other Sowadski JM and Epstein LF (2000) Protein Kinases. Encyclopedia of Life Sciences. London: Nature Publishing Group. http://www.els.net. | |
| book Vallar L, Gullick WJ, Palmero I and Peters G (1996) "Signalling subversion in cancer". In: Parker PJ and Pawson T (eds) Cell Signalling, pp. 324–367. London: Imperial Cancer Research Fund | |
| Web Links | |
| ePath v-Abl Abelson murine leukemia viral oncogene homolog 1 (ABL1); LocusID: 25. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=25 | |
| ePath v-Akt murine thymoma viral oncogene homolog 1 (AKT1); LocusID: 207. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=207 | |
| ePath Breakpoint cluster region (BCR); LocusID: 613. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=613 | |
| ePath Information on different signalling kinases can be retrieved at the ‘Alliance for Cellular Signaling/ Nature (AfCS/Nature)’ at http://www.signaling-gateway.org/molecule/ | |
| ePath Abl: http://www.signaling-gateway.org/molecule/query?afcsid=A000161 | |
| ePath Tpl2: http://www.signaling-gateway.org/molecule/query?afcsid=A000092 | |
| ePath mTOR: http://www.signaling-gateway.org/molecule/query?afcsid=A000094 | |
Copyright © 2000-2013 by John Wiley & Sons, Inc., or related companies. All rights reserved.
