Altered cell signaling helps explain why cells behave abnormally in many diseases. By linking a molecular change (mutation, toxin, or misexpression) to a specific pathway output, you can predict phenotypes such as uncontrolled division, failed metabolism, or abnormal development.

Big idea: pathway output changes cell behavior

A signal transduction pathway converts an outside or internal cue into a cellular response. Disease can result when signaling becomes too strong, too weak, in the wrong cell type, or at the wrong time.

• Common “failure modes”

  • Constitutive activation (pathway stuck “on” without ligand)

  • Loss of responsiveness (pathway cannot be activated)

  • Misregulated duration (signal lasts too long/too briefly)

  • Wrong location (signal occurs in inappropriate tissues or compartments)

Case study: constitutive growth signaling and cancer (Ras/MAPK)

Many cancers involve abnormal signaling through pathways that promote cell cycle entry, growth, and survival, such as Ras/MAPK.

This diagram summarizes the MAPK (ERK) pathway downstream of a growth-factor receptor, showing Ras activation at the membrane followed by the Raf→MEK→ERK phosphorylation cascade. It reinforces the idea that a single upstream “stuck on” component (e.g., Ras-GTP) can amplify signaling into the nucleus and increase expression of proliferation-associated genes. Source

A classic mechanism is a gain-of-function mutation in Ras that reduces its ability to switch off.

• Normal logic of the pathway (simplified)

  • Ligand binds receptor → relay proteins activate Ras → kinase cascade → transcription factors change gene expression

This Reactome pathway diagram presents the Raf/MAP kinase cascade as an annotated network, tracing information flow from activated Ras to RAF, MEK, and ERK and onward to downstream targets. It is useful for exam-style reasoning because it makes clear where pathway dysregulation (overactivation, loss-of-function, or altered feedback) could shift transcriptional output. Source

• Disease mechanism

  • Mutant Ras remains active longer or continuously, even with low/no upstream signal

• Cellular outcomes students should connect to signaling

  • Increased expression of genes that promote cell division

  • Increased survival signaling (reduced apoptosis in contexts where death would normally occur)

  • Expanded clones of cells with the mutation, contributing to tumour formation

In real tumours, constitutive growth signaling often combines with loss of tumour suppressor function, producing stronger changes in phenotype than either alteration alone.

Case study: reduced hormone signaling and metabolic disease (type 2 diabetes)

In type 2 diabetes, cells may show insulin resistance, meaning insulin signaling produces a weaker-than-normal response.

This figure maps the major routes that regulate GLUT4 translocation in skeletal muscle, highlighting insulin-triggered PI3K→Akt signaling that promotes movement of GLUT4-containing vesicles to the plasma membrane. It provides a mechanistic bridge from “weaker signaling output” to the phenotype of reduced glucose uptake and persistently elevated blood glucose. Source

• Key signaling consequence

  • Target tissues (e.g., muscle, liver, fat) respond poorly to insulin, so glucose uptake and storage are reduced

• Disease-relevant cellular response changes

  • Less movement of glucose transporters to the membrane in some cells

  • Altered enzyme activity and gene expression that favor higher blood glucose

• Phenotype connection

  • Persistently elevated blood glucose reflects a mismatch between the hormone signal and the cellular response, not merely a lack of hormone

This illustrates that disease can result from disrupted signaling even when the ligand (insulin) is present.

Case study: toxin-driven pathway hijacking (cholera and cAMP signaling)

Some pathogens cause disease by chemically altering host signaling proteins rather than mutating DNA.

• Core idea

  • A bacterial toxin modifies a host signaling component, producing an abnormally strong second-messenger signal

• Cholera example (high-level logic)

  • Toxin locks a G protein pathway in an “on” state → elevated cAMP → ion transport changes → water follows osmotically

• Observable outcome

  • Excessive fluid loss (watery diarrhoea) is the organism-level phenotype of a misregulated cellular signaling output

This case highlights that altered signaling can be acute, environmental, and reversible if the toxin is removed.

Case study: developmental abnormalities from mis-timed patterning signals (Hedgehog)

During development, signaling pathways act as positional information, turning gene programs on/off in specific places.

• Hedgehog pathway disruption (broad pattern)

  • Too little or too much signaling during a critical window changes which genes are expressed in a developing tissue

• Phenotype link

  • Incorrect tissue patterning can yield structural abnormalities because cells adopt the wrong identities or differentiation programs

Developmental diseases are often explained by where and when signaling is altered, not just whether it is increased or decreased.

Interpreting “case study” evidence on the AP exam

AP Biology commonly expects you to connect molecular changes to phenotypes.

• If a pathway component is stuck “on,” predict:

  • Increased downstream activity (e.g., more phosphorylated targets, more transcription of response genes)

• If a pathway component is nonfunctional, predict:

  • Reduced downstream activity even when ligand is present

• If the phenotype is tissue-specific, consider:

  • Whether the receptor/pathway is expressed in that tissue and during that developmental stage