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Kinase

DRAFT

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Protein kinases function as the cell's central command, they exert remarkable control over a multitude of cellular processes through a seemingly simple mechanism: phosphorylation. By transferring phosphate groups derived from adenosine triphosphate (ATP) to specific amino acids on target proteins, protein kinases trigger a cascade of signaling events that precisely regulate cellular destiny.

Biological relevance

Protein kinases occupy a pivotal position in cellular signaling, translating extracellular cues from hormones and growth factors into intricate intracellular responses. These responses encompass a wide range of essential functions:

  • Signal Transduction: Kinases act as signal transducers, relaying messages received from external stimuli to initiate critical pathways for cell growth, differentiation, and division.
  • Metabolic Control: Protein kinases regulate enzymes involved in energy production and biosynthesis, ensuring efficient cellular metabolism.
  • Cell Cycle Progression: These enzymes precisely control the orderly passage of cells through the various stages of the cell cycle, ensuring proper replication and division.
  • Cell Fate Determination: Protein kinases influence survival, proliferation, or programmed cell death (apoptosis).
  • Gene Expression: Protein kinases can modulate gene expression by regulating transcription factors, dictating which genes are turned on or off in a cell.

Disease development

Given their critical role in cellular control, it's unsurprising that dysregulation of protein kinases can contribute to a multitude of human pathologies:

  • Oncogenesis: Aberrant activation of protein kinases is a hallmark of many cancers. These hyperactive kinases promote uncontrolled cell growth and division, a defining characteristic of the malignant state.
  • Neurodegenerative Disorders: Dysregulation of protein kinases has been implicated in the pathogenesis of Alzheimer's disease, Parkinson's disease, and Huntington's disease.
  • Cardiovascular Diseases: Abnormal protein kinase activity can contribute to the development of heart failure and arrhythmias.
  • Chronic Inflammatory Conditions: Inappropriate activation of protein kinases can underlie chronic inflammatory diseases like arthritis.

As a drug target

The pleiotropic effects of protein kinases on cellular processes make them prime targets for drug development. Their attractiveness as therapeutic targets stems from several key advantages:

  • Specificity: Drugs can be designed to specifically recognize and inhibit the activity of a particular protein kinase, minimizing off-target effects and improving patient outcomes.
  • Diversity: The vast repertoire of protein kinases allows for the targeted modulation of specific signaling pathways implicated in a particular disease.
  • Druggability: Many protein kinases possess structural features that facilitate the development of drugs that can effectively bind and modulate their activity.

Additional readings

  • Fabbro, D., Cowan‐Jacob, S. W., & Moebitz, H. (2015). Ten things you should know about protein kinases: IUPHAR Review 14. British journal of pharmacology, 172(11), 2675-2700. DOI: 10.1111/bph.13096