Protein Kinase Activity in Oncogenic Mechanisms

Protein kinases orchestrate cellular signalling by catalysing phosphorylation, a reversible covalent modification that alters protein activity, interactions and localisation. Dysregulation of kinase activity underlies numerous malignancies. In oncogenic contexts, aberrant activation of tyrosine kinases such as Src and receptor tyrosine kinases drives uncontrolled proliferation, survival and metastatic potential. Mechanistically, gain-of-function mutations or overexpression of kinases induces constitutive downstream signalling through pathways including MAPK, PI3K–AKT and STAT. Viral oncogenes exploit kinase domains to subvert host phosphorylation networks while cellular proto-oncogenes are converted into oncogenes by structural alterations that relieve autoinhibition. Cross-talk between kinase families further amplifies oncogenic cascades, exemplified by PKC-mediated modulation of RTK activity. The global significance of kinase dysregulation has spurred the development of small-molecule inhibitors, which target ATP-binding pockets or regulatory domains, transforming cancer therapeutics.

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Protein Kinase Activity in Oncogenic Mechanisms publication trend

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Technical terms

Protein kinase: An enzyme that transfers phosphate groups from ATP to specific amino acids on proteins, modulating their function.

Tyrosine kinase: A class of protein kinases that specifically phosphorylate tyrosine residues, often involved in growth and differentiation signalling.

Oncogene: A gene that has the potential to cause cancer, typically encoding proteins that regulate cell growth or death.

Receptor dimerisation: The association of two receptor molecules, a critical step in activation of many receptor tyrosine kinases.

SH3 domain: A modular protein domain that mediates interaction with proline-rich motifs, important for substrate recognition and localisation.

References

1. Analysis of the catalytic domain of phosphotransferase activity of two avian sarcoma virus-transforming proteins.. Journal of Biological Chemistry (1984).
2. Phosphorylation sites in enolase and lactate dehydrogenase utilized by tyrosine protein kinases in vivo and in vitro.. Journal of Biological Chemistry (1984).
3. A Protein Tyrosine Kinase Involved in Regulation of pp60c-src function*. Journal of Biological Chemistry (1989).
4. Biological role of epidermal growth factor-receptor clustering. Investigation with monoclonal anti-receptor antibodies.. Journal of Biological Chemistry (1983).
5. C-kinase phosphorylates the epidermal growth factor receptor and reduces its epidermal growth factor-stimulated tyrosine protein kinase activity.. Journal of Biological Chemistry (1984).