Changes in Signal Transduction Pathways

Because signal transduction pathways involve many discrete molecular steps, an error at any single step can alter the entire outcome of the pathway. A mutation could change a receptor's shape so it can no longer bind its ligand (loss of reception), disable a relay protein so the cascade stalls partway through (loss of transduction), or alter a transcription factor so the wrong genes are turned on (altered response).

Conversely, mutations can also cause a pathway component to become permanently or excessively active - for instance, a receptor tyrosine kinase that dimerizes and signals even without ligand present, or a G-protein locked in its active, GTP-bound form because it can no longer hydrolyze GTP.

Signal transduction pathways can also be disrupted by molecules from outside the organism. Environmental toxins, venoms, and pharmaceutical drugs frequently work by mimicking, blocking, or otherwise interfering with normal signaling: for example, some toxins permanently activate G-proteins, and many drugs are designed specifically as receptor agonists (activate) or antagonists (block) to therapeutically alter a pathway's activity.

Because these external chemicals interact with the same reception, transduction, or response steps used in normal signaling, understanding the wiring of a pathway lets researchers predict where a given toxin or drug will act and what downstream effects to expect.

When signal transduction is altered, the cellular and organismal consequences depend on which pathway is affected and how. Mutations in growth-factor signaling pathways that cause constitutive activation are a major cause of cancer, since cells receive a continuous 'divide' signal even without any external growth factor present.

Other disrupted pathways cause different diseases: insulin receptor pathways that no longer respond properly to insulin binding lead to insulin resistance and type 2 diabetes, while pathways controlling ion channels, if disrupted, can cause disorders of the nervous or muscular systems. Not all changes are pathological, however - natural variation in signaling pathway components also contributes to normal phenotypic diversity between individuals.