Signal Transduction Study Guide PDF

Signal Transduction Study Guide Signal Transduction Overview Definition: The process of converting information into a chemical change. ○ Signal: Detected by specific receptors. ○ Conversion: Involves a chemical process to generate a cellular response. General Features of...

Signal Transduction Study Guide Signal Transduction Overview Definition: The process of converting information into a chemical change. ○ Signal: Detected by specific receptors. ○ Conversion: Involves a chemical process to generate a cellular response. General Features of Signal Transduction 1. Specificity: Achieved by molecular complementarity between signal and receptor molecules (non-covalent interactions). 2. Sensitivity: High receptor affinity for ligands (dissociation constant Kd < 10⁻⁷ M). 3. Amplification: Enzyme cascades amplify the signal. 4. Integration: System integrates multiple signals to produce a unified response. 5. Localization: Signaling components are confined to specific cellular structures for localized responses. Common Features of Signal Transduction Modularity: ○ Proteins have multiple domains for recognizing features. ○ Scaffold Proteins: Non-enzymatic proteins that assemble interacting enzymes. Desensitization: ○ Receptors can become unresponsive to persistent signals. Divergence: ○ Signals often branch out for diverse responses. Types of Cellular Signals Cells respond to: Hormones, neurotransmitters, growth factors, nutrients, odorants, light, tastants, extracellular matrix components, and more. Basic Components of Signal Transduction  Plasma membrane receptors (e.g., GPCRs). G proteins (bind GTP or GDP). Effector enzymes (e.g., adenylyl cyclase). Protein kinases and phosphatases. Steps in Signal Transduction 1. Signal (ligand) binds receptor. 2. Activated receptor produces second messengers or protein activity changes. 3. Cellular response occurs. 4. Signal transduction ends. G Protein-Coupled Receptors (GPCRs) 1. Definition: Largest family of plasma membrane receptors. 2. Components: ○ Receptor with 7 transmembrane helices. ○ G protein (active: GTP-bound, inactive: GDP-bound). ○ Effector enzyme or ion channel. 3. Mechanism: ○ First messenger binds receptor → activates G protein → G protein activates effector enzyme → produces second messengers (e.g., cAMP). 4. Second Messengers: ○ Examples: cAMP, Ca²⁺, IP₃, diacylglycerol. ○ Regulate downstream signaling targets. β-Adrenergic Receptor System Ligand: Epinephrine binds to β-adrenergic receptors. Pathway: ○ GPCR activates G protein (Gs). ○ Gs activates adenylyl cyclase → produces cAMP. ○ cAMP activates PKA (protein kinase A) → phosphorylates target proteins. Termination: ○ Decrease in epinephrine concentration. ○ GTP hydrolysis by G protein. ○ cAMP hydrolyzed to 5'-AMP by phosphodiesterase. Key Terms Agonist: Mimics natural ligand effects. Antagonist: Blocks receptor activity. GTPase Switch: G proteins deactivate by hydrolyzing GTP → GDP. CREB: Transcription factor phosphorylated by PKA to regulate gene expression. Phospholipase C, IP₃, and Ca²⁺ Signaling 1. Phospholipase C (PLC): Cleaves PIP₂ into: ○ Diacylglycerol (DAG): Activates protein kinase C (PKC). ○ IP₃: Releases Ca²⁺ from intracellular stores. 2. Ca²⁺: Acts as a second messenger. Defects in Signal Transduction Ras Mutations: Disrupt GTPase activity, leading to uncontrolled signaling and cancer. Activating Mutations: Elevated cAMP levels (e.g., in adenomas). Inactivating Mutations: Impaired responses to hormonal signals. Regulation and Adaptation in Signal Transduction 1. Desensitization: ○ Receptors phosphorylated (e.g., by β-adrenergic receptor kinase). ○ Arrestin binding blocks G protein interaction. 2. Adaptor Proteins: ○ Confine signaling molecules to specific regions. ○ Example: AKAPs (A kinase anchoring proteins). Summary of Signal Transducers 1. GPCRs: Coupled with G proteins, act via cAMP or other second messengers. 2. Receptor Tyrosine Kinases: Phosphorylate target proteins on Tyr residues. 3. Ligand-Gated Ion Channels: Direct ion flow. 4. Intracellular Receptors: Bind lipophilic signals (e.g., steroids). Study Tip Focus on understanding the common themes in signal transduction: specificity, amplification, integration, modularity, and termination. Study Guide: Key Concepts in Cell Signaling 1. Mutations in Gα Protein Activating Mutations: ○ Lead to continuously elevated cAMP levels. ○ Found in ~40% of adenomas. Inactivating Mutations: ○ Cause unresponsiveness to hormones that use cAMP as a second messenger. 2. Second Messengers: Diacylglycerol, IP3, and Ca²⁺ Phospholipase C (PLC): ○ Cleaves PIP₂ (phosphatidylinositol 4,5-bisphosphate) into diacylglycerol and inositol 1,4,5-triphosphate (IP₃). Signals Using PLC/IP₃/Ca²⁺ Pathway: ○ Includes acetylcholine, gastrin-releasing peptide, angiotensin II, histamine, vasopressin, and oxytocin. Role of IP₃: ○ Opens IP₃-gated Ca²⁺ channels in the ER, releasing Ca²⁺ into the cytosol. Activation of Protein Kinase C (PKC): ○ Diacylglycerol and elevated Ca²⁺ levels activate PKC. Calcium as a Second Messenger: ○ Cytosolic Ca²⁺ is tightly regulated by pumps and is elevated in response to stimuli. ○ Calmodulin (CaM) binds Ca²⁺, changing conformation to regulate various proteins (e.g., CaM kinases). 3. G Protein-Coupled Receptors (GPCRs) in Vision, Olfaction, and Taste Vision: ○ Rhodopsin: A GPCR in rod cells with 11-cis-retinal as its chromophore. ○ Rhodopsin Kinase and Arrestin: Desensitize activated rhodopsin. Olfaction: ○ Golf Protein: Triggers cAMP-gated ion channels, leading to action potentials. Taste: ○ Gustducin: Stimulates cAMP production and affects K⁺ channel phosphorylation. 4. Common Features of GPCR Signaling Seven-transmembrane helices, intrinsic GTPase activity, cyclic nucleotides, and protein kinases are central to signaling. GPCRs are encoded in many species, including humans (~800 genes). 5. Receptor Tyrosine Kinases (RTKs) Structure: ○ Extracellular ligand-binding domain and cytoplasmic tyrosine kinase domain. Insulin Receptor Activation: ○ Dimer of αβ monomers; autophosphorylation of Tyr residues activates kinase activity. Signal Cascade: ○ IRS1 binds phosphorylated Tyr residues, initiating signaling pathways like the MAPK cascade. ○ PI3K activation leads to PIP₂ to PIP₃ conversion, GLUT4 translocation, and glycogen synthase activation. 6. Ion Channels and Electrical Signaling Gated Ion Channels: ○ Respond to ligands or voltage changes; regulate Na⁺, K⁺, Cl⁻, and Ca²⁺ flux. Action Potentials: ○ Generated by voltage-gated Na⁺ influx and K⁺ efflux, propagating electrical signals along neurons. Receptor Channels: ○ Ionotropic Receptors: Directly gated ion channels. ○ Metabotropic Receptors: Indirectly trigger second messenger pathways. Key Tables for Review Table 12-4: Signals that activate the PLC/IP₃/Ca²⁺ pathway. Table 12-5: Proteins regulated by Ca²⁺ and calmodulin (e.g., adenylyl cyclase, nitric oxide synthase, myosin light-chain kinase). Key Terms Autophosphorylation: Self-phosphorylation of RTKs to activate downstream signaling. MAPK Cascade: Amplifies growth factor signals (Raf-1 → MEK → ERK). Calmodulin (CaM): Regulates enzymes via Ca²⁺ binding. Second Messengers: Molecules like cAMP, IP₃, and Ca²⁺ that mediate intracellular signaling. This guide highlights the essential information for understanding the signaling pathways and mechanisms described.