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Cell Signaling pathways can control critical cellular functions and play crucial roles in development and immune response.

 

Cell Signaling

  • Cell signaling refers to the translation of an external signal into a cell’s response
  • When a ligand binds a receptor, it triggers intracellular signaling relays of secondary messenger molecules
  • Many signaling pathways involve proteins called kinases. Kinases can exist in ‘on’ and ‘off’ states of activation
  • Many signaling pathays influence gene expression that can be mediated via changes to transcription factors

Pathway functions

  • Hormone-driven pathways

    Estrogen receptor (ER), androgen receptor (AR), glucocorticoid receptor (GR)

  • Growth factor pathways

    PI3K, MAPK, JAK-STAT1/2, JAK-STAT3

  • Development pathways

    TGFβ, Notch, Hedgehog (Hh), Wnt

  • Immune pathways

    JAK-STAT1/2, NF-КB

Aberrant single pathways or cooperation or crosstalk between multiple pathways (MAPK + TGFβ) are know to cause disease.

Aberrant pathway signaling is linked to diseases across almost all major therapeutic areas.

Signaling pathways are extremely dynamic –
requiring a ‘systems’ approach to analysis.

Signaling & Disease

  • DNA mutations do not necessarily cause at aberrant signaling, yet aberrant signaling may result in disease
    • Cancer cells have constant activation of signaling cells to grow and divide. This often occurs because of mutations in receptors, protein kinases or transcription factors
    • Some immunodeficiencies occur because immune cells lack either the receptors for ligands that instruct immune cells to divide and develop the specific kinases that transmit these signals
  • Specific target mutations, e.g., PIK3CA are not required for oncogenic signaling and thus may not determine disease progression or drug response
  • Untreated cooperative pathways may also drive drug resistance

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