Oncogenic Kinases in Cancer


Oncogenesis involves the generation and transmission of signals that result in de‐regulation 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. Such kinases transfer phosphates to tyrosine residues or serine and threonine residues of other kinases or proteins that participate in various signalling pathways in the cell. Up to 20% of the 32 000 human genes sequenced by the Human Genome Project encode proteins that are involved in cellular signalling, and among these, more than 520 are protein kinases. Many of these kinases have been implicated in tumorigenesis involving transmembrane, cytoplasmic and nuclear signalling, cell‐cycle control and regulation of apoptosis. Screening and targeting oncogenic kinases are becoming rapidly part of a personalised strategy for the treatment of cancer.

Key Concepts

  • Oncogenic receptor kinases.
  • Cytoplasmic and nuclear signalling oncogenic kinases.
  • Oncogenic kinases involved in cell‐cycle control.
  • Kinases contribute to oncogenesis by regulating apoptosis.
  • Targeting kinases is a viable strategy for cancer therapy.

Keywords: tyrosine kinases; receptor kinases; serine/threonine kinases; cell cycle; apoptosis

Figure 1. Receptor tyrosine kinases mediate extra‐cellular 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; Iκkα, IκB kinase α NIK, NfκB activating–interleukin1 receptor–induced kinase; IκB, inhibitor of NFκ B; RelA, subunit of Nfκ B, p50 nuclear factor κ B subunit; NFκB, nuclear factor κ 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, extra‐cellular 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.


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Further Reading

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Web Links

Abl: http://www.signaling‐gateway.org/molecule/query?afcsid=A000161

Information on different signalling kinases can be retrieved at the ‘Alliance for Cellular Signaling/Nature (AfCS/Nature)’ at http://www.signaling‐gateway.org/molecule/

Tpl2: http://www.signaling‐gateway.org/molecule/query?afcsid=A000092

mTOR: http://www.signaling‐gateway.org/molecule/query?afcsid=A000094

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Tsintarakis, Antonis, and Zafiropoulos, Alexandros(Sep 2017) Oncogenic Kinases in Cancer. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0006051.pub3]