4.2 Introduction to Signal Transduction

Signal transduction is how cells turn an external chemical signal (a ligand) into a specific response inside the cell. It starts when a ligand binds a receptor (surface receptors like G protein–coupled receptors or receptor tyrosine kinases, or intracellular receptors for small hydrophobic ligands). Ligand binding changes the receptor’s shape (conformational change), triggering a signaling cascade: G proteins, enzymes (like adenylyl cyclase), second messengers (cAMP), and protein kinases activate downstream targets. Phosphorylation cascades (e.g., MAP kinase pathway) amplify the signal; phosphatases turn signals off. Outcomes include changes in ion channel opening, secretion, metabolism, or gene expression. This topic is tested on the AP exam under LO 4.2.A/B—know receptor types, second messengers, amplification, and phosphorylation. For a concise review, see the Topic 4.2 study guide (https://library.fiveable.me/ap-biology/unit-4/intro-signal-transduction/study-guide/VAotQCiNsYQzCcmUBt3D). For broader Unit 4 review and lots of practice Qs (1000+), check the unit page (https://library.fiveable.me/ap-biology/unit-4) and practice problems (https://library.fiveable.me/practice/ap-biology).

Cells need signal transduction pathways so they can detect outside signals (ligands) and turn those into specific inside actions. Receptors (surface or intracellular) bind a ligand and change shape, starting a cascade of events—often involving second messengers (like cAMP), protein kinases, and phosphorylation cascades—that relay and amplify the signal. Amplification means one ligand can trigger many downstream enzymes, producing big changes such as altered gene expression, secretion, or cell growth. Pathways also let cells integrate multiple signals and turn them off (phosphatases), so responses are regulated and context-specific. This is exactly what LO 4.2.A/B covers on the AP CED: components (ligand, receptor, second messenger) and mechanisms (amplification, phosphorylation). Review the Topic 4.2 study guide for examples and diagrams (https://library.fiveable.me/ap-biology/unit-4/intro-signal-transduction/study-guide/VAotQCiNsYQzCcmUBt3D), check the Unit 4 overview (https://library.fiveable.me/ap-biology/unit-4) and practice more AP-style problems (https://library.fiveable.me/practice/ap-biology) to prep for exam questions.

A ligand is the chemical messenger—a molecule (like a peptide hormone or small molecule) that fits into a receptor’s ligand-binding domain. A receptor is a protein (on the plasma membrane or inside the cell) that specifically recognizes and binds that ligand. Binding triggers a conformational change in the receptor’s intracellular domain, starting signal transduction: G protein–coupled receptors or receptor tyrosine kinases activate downstream enzymes, second messengers (like cAMP), and phosphorylation cascades to amplify the signal and produce responses (e.g., gene expression, secretion, or ion-channel opening). In short: ligand = the signal; receptor = the sensor that receives the signal and starts the pathway (EK 4.2.B.1–2). For a quick AP-level review, see the Topic 4.2 study guide (https://library.fiveable.me/ap-biology/unit-4/intro-signal-transduction/study-guide/VAotQCiNsYQzCcmUBt3D). For extra practice, check the unit and practice question pages (https://library.fiveable.me/ap-biology/unit-4 and https://library.fiveable.me/practice/ap-biology).

When a ligand (a specific chemical messenger) binds a receptor protein, the receptor’s ligand-binding domain recognizes it and the receptor changes shape (a conformational change). If the receptor’s on the plasma membrane (like a G protein–coupled receptor, receptor tyrosine kinase, or ligand-gated ion channel) that shape change either activates a G protein, autophosphorylates tyrosines, or opens/closes an ion channel. If the receptor is inside the cell (intracellular receptor), the ligand must cross the membrane first. After activation, the receptor starts a signal transduction cascade: enzymes, protein kinases, and second messengers (like cAMP produced by adenylyl cyclase) relay and amplify the signal. That can trigger a phosphorylation cascade (e.g., MAP kinase pathway), change enzyme activity, move proteins to the membrane, or alter gene expression. Phosphatases turn signals off. This chain—reception → transduction → response—is exactly what the AP CED expects you to describe (see LO 4.2.A/B). For a quick review, check the Topic 4.2 study guide (https://library.fiveable.me/ap-biology/unit-4/intro-signal-transduction/study-guide/VAotQCiNsYQzCcmUBt3D) and try practice questions (https://library.fiveable.me/practice/ap-biology).

A G protein–coupled receptor (GPCR) is a cell-surface receptor protein that detects an external ligand and starts an internal signaling cascade (EK 4.2.B.1–2). Structurally it spans the membrane seven times (7 transmembrane helices) and has an extracellular ligand-binding domain and an intracellular domain that changes shape after ligand binding. That conformational change lets the receptor activate a nearby G protein by promoting GDP → GTP exchange on the α subunit. The G protein dissociates and the active subunits regulate effectors (e.g., adenylyl cyclase), producing second messengers like cAMP. cAMP activates protein kinase A, leading to phosphorylation cascades that amplify the signal and produce responses (gene expression, secretion, growth) (EK 4.2.A.2; EK 4.2.B.2). GPCRs are a major AP topic (LO 4.2.B); review the Topic 4.2 study guide for diagrams and practice (https://library.fiveable.me/ap-biology/unit-4/intro-signal-transduction/study-guide/VAotQCiNsYQzCcmUBt3D). For broader unit review and lots of practice questions, see the unit page (https://library.fiveable.me/ap-biology/unit-4) and practice bank (https://library.fiveable.me/practice/ap-biology).

A phosphorylation cascade is a chain reaction that relays a signal from a receptor to a cellular response by sequentially adding phosphate groups to proteins. After a ligand binds (e.g., to a receptor tyrosine kinase or GPCR), the receptor changes shape and activates a protein kinase (or a G protein that activates adenylyl cyclase → cAMP → PKA). That first kinase phosphorylates downstream kinases, each one activating the next—often culminating in MAP kinase activation that changes enzyme activity or turns on transcription factors to alter gene expression. Cascades amplify signals (one kinase can phosphorylate many targets) and speed responses. Phosphatases reverse phosphorylation to shut the signal off. This process directly maps to LO 4.2.A/B and EK 4.2.A.1–A.2 and EK 4.2.B.2 in the CED. For a compact AP-aligned review, see the Topic 4.2 study guide (https://library.fiveable.me/ap-biology/unit-4/intro-signal-transduction/study-guide/VAotQCiNsYQzCcmUBt3D) and practice questions (https://library.fiveable.me/practice/ap-biology).

Surface vs. intracellular receptors differ mainly in ligand type and where the signal starts. Surface receptors (GPCRs, receptor tyrosine kinases, ligand-gated ion channels) sit in the plasma membrane and bind hydrophilic ligands (peptides, neurotransmitters). Ligand binding causes a conformational change in the receptor’s intracellular domain, activating G-proteins, kinases, or ion flow and launching phosphorylation cascades and second-messenger signals (cAMP, MAP kinase)—fast amplification and diverse responses like secretion or altered metabolism (EK 4.2.B.1–2). Intracellular receptors (cytoplasm or nucleus) bind small hydrophobic ligands (steroid or thyroid hormones) that cross the membrane; the receptor–ligand complex often directly alters gene transcription and slower, longer-term responses. Remember: location determines mechanism—surface = signal relay/amplification; inside = direct gene regulation. For a quick AP-aligned review, check the Topic 4.2 study guide (https://library.fiveable.me/ap-biology/unit-4/intro-signal-transduction/study-guide/VAotQCiNsYQzCcmUBt3D) or the Unit 4 overview (https://library.fiveable.me/ap-biology/unit-4) and try practice questions (https://library.fiveable.me/practice/ap-biology).

Signal amplification happens so a small amount of ligand binding gives a big, fast cellular response—cells need to respond to tiny signals (hormones, neurotransmitters) without requiring huge amounts of ligand. It works through cascades: a ligand binds a receptor (GPCR or RTK), the receptor changes shape and activates an enzyme or G protein. That activated protein then activates many downstream enzymes (kinases) in a phosphorylation cascade (e.g., MAP kinase pathway). Each kinase phosphorylates many target proteins, so one activated upstream molecule yields many active downstream molecules. Second messengers (cAMP made by adenylyl cyclase) also amplify because one enzyme makes many cAMP molecules, and each cAMP activates multiple protein kinase A molecules. Phosphatases can turn the signal off. This amplification idea is in the CED (EK 4.2.B.2)—review the Topic 4.2 study guide on Fiveable (https://library.fiveable.me/ap-biology/unit-4/intro-signal-transduction/study-guide/VAotQCiNsYQzCcmUBt3D) and more unit resources (https://library.fiveable.me/ap-biology/unit-4). For extra practice, try the Fiveable AP problems (https://library.fiveable.me/practice/ap-biology).

cAMP (cyclic AMP) is a small intracellular second messenger made from ATP by the enzyme adenylyl cyclase after a receptor (often a G protein–coupled receptor) is activated by a ligand. It’s important because it relays and amplifies signals inside the cell: cAMP binds and activates protein kinase A (PKA), which phosphorylates target proteins and can trigger phosphorylation cascades that change enzyme activity, ion channels, or gene expression. That amplification (one receptor → many G proteins → many adenylyl cyclase molecules → lots of cAMP) lets a small external signal produce a big cellular response, which is exactly what EK 4.2.B.2 and EK 4.2.B.2.ii describe. On the AP exam, expect questions about cAMP’s role as a second messenger, its production by adenylyl cyclase, and downstream activation of PKA (see the Topic 4.2 study guide for a quick review) (https://library.fiveable.me/ap-biology/unit-4/intro-signal-transduction/study-guide/VAotQCiNsYQzCcmUBt3D). For more practice, try problems in the Unit 4 practice set (https://library.fiveable.me/practice/ap-biology).

Hormones usually travel through the bloodstream to reach target cells—that’s the long-distance signaling the CED calls out (EK 4.2.B.3). Endocrine cells secrete hormones into blood; the hormone diffuses or is carried (some steroid and thyroid hormones bind carrier proteins) until it encounters a target cell. Whether the receptor’s on the plasma membrane or inside the cell depends on the hormone type (EK 4.2.B.1.iii): peptide hormones (e.g., insulin) are water-soluble and bind surface receptors (often triggering G-protein or tyrosine kinase cascades and second messengers like cAMP), while lipid-soluble steroid hormones cross the membrane and bind intracellular receptors that alter gene expression. Local signals exist too (paracrine/autocrine) when the messenger acts nearby. On the AP exam, be ready to connect “hormone → receptor location → conformational change → signal transduction/amplification → cell response” (see Topic 4.2 study guide (https://library.fiveable.me/ap-biology/unit-4/intro-signal-transduction/study-guide/VAotQCiNsYQzCcmUBt3D)). For more review, check the Unit 4 overview (https://library.fiveable.me/ap-biology/unit-4) and practice questions (https://library.fiveable.me/practice/ap-biology).

When a ligand binds a ligand-gated channel (a receptor protein), the channel undergoes a conformational change that either opens or closes the pore (EK 4.2.B.2.i and iv). If it opens, specific ions (e.g., Na+, K+, Ca2+, Cl−) flow down their electrochemical gradients into or out of the cell, changing membrane potential and quickly initiating a cellular response. If it closes, ion flow stops and the electrical/chemical signals are altered. These ion movements can directly change cell excitability (nerve/muscle) or trigger downstream signaling (e.g., Ca2+ acting as a second messenger), linking reception to response (EK 4.2.A.1; EK 4.2.B.2.ii). For a quick review, check the Topic 4.2 study guide (https://library.fiveable.me/ap-biology/unit-4/intro-signal-transduction/study-guide/VAotQCiNsYQzCcmUBt3D) and more unit resources (https://library.fiveable.me/ap-biology/unit-4). Practice questions are here: (https://library.fiveable.me/practice/ap-biology).

Think of a single signal (ligand) like a starting domino—the receptor it binds to converts that one event into many molecular changes. First, receptor type and location matter: surface receptors (GPCRs, RTKs, ligand-gated ion channels) vs. intracellular receptors lead to different immediate effects (ion flow, enzyme activation, or direct gene regulation). Second, amplification: one activated receptor can activate many G proteins or enzyme molecules; each of those makes lots of second messengers (like cAMP), so one ligand → thousands of intracellular signals. Third, cascades and branching: phosphorylation cascades (MAP kinase pathways, protein kinases) pass and amplify signals and can branch to multiple targets (metabolic enzymes, cytoskeleton, transcription factors). Fourth, cell context: different cells express different receptors, kinases, phosphatases, and transcription factors, so the same signal gives different responses (secretion, growth, gene expression). For AP review, focus on ligand → receptor → second messenger → phosphorylation cascade → response (see the Topic 4.2 study guide: https://library.fiveable.me/ap-biology/unit-4/intro-signal-transduction/study-guide/VAotQCiNsYQzCcmUBt3D). Practice questions here: https://library.fiveable.me/practice/ap-biology.

Second messengers are small, nonprotein molecules or ions that transmit signals from an activated receptor inside the cell. When a ligand binds a membrane receptor (often a G protein–coupled receptor or receptor tyrosine kinase), the receptor changes shape and activates enzymes like adenylyl cyclase or phospholipase C. Those enzymes make second messengers such as cyclic AMP (cAMP), Ca2+, IP3, or DAG. Second messengers diffuse quickly, amplify the signal (one receptor can produce many cAMP molecules), and activate downstream effectors—for example, cAMP activates protein kinase A, and Ca2+ can activate kinases or other proteins—leading to phosphorylation cascades and cellular responses (secretion, gene expression, growth). This fits EK 4.2.B.2 and EK 4.2.A.2 in the CED. For a quick Topic 4.2 review, see the Fiveable study guide (https://library.fiveable.me/ap-biology/unit-4/intro-signal-transduction/study-guide/VAotQCiNsYQzCcmUBt3D) and practice questions (https://library.fiveable.me/practice/ap-biology).

Phosphorylation (adding a phosphate group) is a fast, reversible way to change a protein’s shape and activity after a receptor is activated. Protein kinases transfer phosphates to target proteins, turning enzymes or transcription factors on/off and creating a phosphorylation cascade (e.g., MAP kinase pathway) that amplifies the original signal—one activated kinase can activate many downstream kinases. Phosphatases remove phosphates to shut the signal off. This lets cells relay a small external ligand binding event into big responses (change gene expression, secretion, or cell growth) and provides control points for timing and specificity. On the AP exam, expect to connect ligand → receptor conformational change → kinases/second messengers (like cAMP) → phosphorylation cascade → cellular response (EK 4.2.A.1, EK 4.2.A.2, EK 4.2.B.2). For extra review, check the Topic 4.2 study guide (https://library.fiveable.me/ap-biology/unit-4/intro-signal-transduction/study-guide/VAotQCiNsYQzCcmUBt3D) and practice questions (https://library.fiveable.me/practice/ap-biology).

Receptors are placed where they can “see” their ligand and make the right response. Hydrophilic ligands (peptides, most proteins) can’t cross the plasma membrane, so their receptors are on the cell surface (GPCRs, receptor tyrosine kinases, ligand-gated channels). Those membrane receptors change shape, start phosphorylation cascades and second-messenger signaling (cAMP, MAPK) to give fast or amplified responses (EK 4.2.B.1–B.2). Small lipophilic signals (steroid, thyroid hormones) cross the membrane, so their receptors are inside the cell—in the cytoplasm or nucleus. Those intracellular receptors often act as transcription factors to directly change gene expression, producing slower but long-lasting effects. Location therefore matches ligand chemistry and the type of cellular response (rapid signaling vs altering gene expression). For AP exam review, see Topic 4.2 study guide (https://library.fiveable.me/ap-biology/unit-4/intro-signal-transduction/study-guide/VAotQCiNsYQzCcmUBt3D) and practice questions (https://library.fiveable.me/practice/ap-biology).