Cell Signaling: Mechanisms, Receptors, and Pathways in Biology

Cell communication

The ability of cells to receive, process, and transmit signals with their environment and with one another; essential for coordinating cellular activities.

Cellular signaling

Involves ligands (signaling molecules), receptors that bind them, and a resulting cellular response through signal transduction.

Ligand

A signaling molecule that specifically binds to a receptor to trigger a cellular response.

Receptor

A protein molecule that binds a specific ligand and initiates a signal transduction pathway.

Response

The final cellular activity triggered by a signal, such as gene activation, enzyme regulation, or structural change.

Signal transduction

The process by which a signal from outside the cell is converted into a functional change inside the cell.

Analogy: Doorbell system

Signal = button press; sensor = doorbell detects press; wire/phosphate = carries signal; response regulator = rings chime (DNA/gene response); reset = chime stops.

Cell signaling in prokaryotes

A molecule (nutrient, stress cue, autoinducer) activates a sensor kinase that autophosphorylates and transfers the phosphate to a response regulator, which binds DNA to turn genes on or off.

Steps of prokaryotic signaling

1 Signal detected → 2 Sensor kinase phosphorylates itself → 3 Phosphate transferred to response regulator → 4 Regulator activates/represses DNA → 5 Cell changes behavior → 6 System resets.

Biofilm

A thick, structured community of prokaryotes forming a protective colony on a surface.

Quorum sensing

Bacterial communication that allows a population to coordinate gene expression once a critical density is reached.

Importance of quorum sensing

Enables stress survival, biofilm formation, and activation of virulence genes at the right time.

Inducer (in eukaryotic signaling)

A tissue or cell that releases a signal changing the behavior of another tissue or cell.

Competence

The ability of a cell or tissue to respond to an inducing signal.

Intercellular signaling

Communication between different cells.

Intracellular signaling

Communication within a single cell between its own compartments or molecules.

Paracrine signaling

Local signaling where one cell releases molecules that act on nearby target cells.

Synaptic signaling

Specialized local signaling where neurotransmitters cross a synapse between nerve cells.

Autocrine signaling

A cell releases signals that bind to receptors on its own surface, affecting itself.

Endocrine signaling

Long-distance signaling using hormones transported through the bloodstream to target cells.

Contact-dependent signaling (juxtacrine)

Direct physical contact between cells through membrane-bound molecules (e.g., cadherins and receptor proteins).

Cell junctions

Structures that connect adjacent cells, allowing communication or transport of signaling molecules.

Cell-cell recognition

Interaction between cell-surface molecules that allows cells to identify and respond to each other.

Growth factor

A signaling molecule that stimulates cell growth and division via receptor activation.

Cadherin

A calcium-dependent adhesion protein important for cell-cell contact and signaling.

Actin microfilament-associated proteins

Link surface receptors to the cytoskeleton for structural and signaling functions.

Local signaling

Communication between nearby cells through short-range molecules such as growth factors or neurotransmitters.

Long-distance signaling

Involves hormones traveling through the bloodstream to distant target cells.

Steps of cellular signaling

1 Reception → 2 Transduction → 3 Response.

Reception

The binding of a ligand to its specific receptor on or inside the cell.

Transduction

A cascade of intracellular reactions that relay and amplify the signal from the receptor to target molecules.

Response (cellular)

The specific physiological change or gene expression triggered by the signaling pathway.

Relay molecules

Intracellular molecules that pass and amplify the signal during transduction.

Types of signaling molecules

Hormones, neurotransmitters, and cytokines.

Hormone

A chemical signal secreted by glands that travels long distances to affect target cells.

Neurotransmitter

A chemical messenger that transmits signals across a synapse from one neuron to another.

Cytokines

Immune system signaling molecules that regulate inflammation, cell differentiation, and immune responses.

Three main types of membrane receptors

G protein-coupled receptors (GPCRs), receptor tyrosine kinases (RTKs), and ion channel receptors.

Cell-surface receptors

GPCRs, RTKs, and ion channels that detect extracellular signals.

Intracellular receptors

Found inside the cell; bind lipid-soluble signals such as steroid hormones.

Steroid hormone receptors

Intracellular receptors that, when bound to hormone, directly influence gene expression.Three stages of cell signaling + Reception, Transduction, and Response.

Reception

The target cell detects a signaling molecule (ligand) when it binds to a receptor protein on or in the cell.

Three main types of membrane receptors

G protein-coupled receptors (GPCRs), receptor tyrosine kinases (RTKs), and ion channel receptors.

G protein-coupled receptor (GPCR)

A cell-surface receptor that works with the help of a G protein; activates GTP-binding proteins to trigger signal cascades.

Examples of GPCRs

Thyroid-stimulating hormone receptor, luteinizing hormone receptor, follicle-stimulating hormone receptor.

Receptor tyrosine kinases (RTKs)

Membrane receptors that attach phosphates to tyrosines; form dimers when activated by a ligand.

Examples of RTKs

Insulin receptor, epidermal growth factor (EGF), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF).

Abnormal RTKs

Mutated RTKs that activate without ligands can cause uncontrolled cell division and contribute to cancers.

Ion channel receptor

A membrane protein that acts as a gate; opens or closes when a ligand binds, allowing ions to flow across the membrane.

Ligand-gated ion channel

Receptor that changes shape upon ligand binding, opening to allow specific ions (e.g., Na⁺, Ca²⁺) to pass through.

Transduction

Converts the signal from receptor binding into a specific cellular response through a cascade of molecular interactions.

Phosphorylation cascade

Series of protein kinases that activate each other sequentially by adding phosphate groups, amplifying the signal.

Protein kinases

Enzymes that transfer phosphate groups from ATP to proteins, activating or deactivating them.

Protein phosphatases

Enzymes that remove phosphate groups, inactivating proteins and turning off signal pathways.

Second messengers

Small, non-protein molecules that spread and amplify the signal within the cell; examples include cAMP, Ca²⁺, and IP₃.

Common second messengers

Cyclic AMP (cAMP) and calcium ions (Ca²⁺).

Signal amplification

One ligand can activate many molecules in a cascade, resulting in a large cellular response.

Scaffolding proteins

Large relay proteins that organize other signaling components, increasing efficiency of the transduction pathway.

Specificity of cell signaling

Each cell type has unique receptor and relay molecule combinations, producing specific responses to the same signal.

Regulation of the response

Signals are not simply "on" or "off"; cells fine-tune responses through amplification, specificity, scaffolding, and termination.

Termination of the signal

Signal stops when ligand concentration decreases, receptors become inactive, or phosphatases remove phosphate groups.

Cytoplasmic response

Rapid regulation of enzyme activity or metabolism (e.g., glycogen breakdown by epinephrine).

Example of cytoplasmic response

Epinephrine binding triggers glycogen breakdown in liver cells, releasing glucose into the bloodstream.

Nuclear response

Slower process involving activation or repression of specific genes to produce new proteins.

Example of nuclear response

Growth factor activation leads to transcription factor phosphorylation, stimulating gene expression.

Receptor regulation

Pathways involving gene expression are slow; those affecting enzyme activity are faster.

Apoptosis

Programmed cell death; integrates multiple signaling pathways to safely dismantle and recycle cellular components.

Molecular basis of apoptosis in C. elegans

Controlled by signals that either promote or inhibit cell death depending on the presence of death signals.

Diseases related to signaling malfunctions

Diabetes, Alzheimer's disease, hypertension, epilepsy, cancer, and heart disease.

Endocrine signaling

Long-distance signaling where hormones travel through the bloodstream to affect distant target cells.

Drug resistance in signaling pathways

Some cancer cells resist targeted drugs due to mutations in transduction pathways or receptor alterations.