Direct cell-to-cell contact signaling. A membrane-bound signal on one cell binds to a receptor on an adjacent cell. Requires physical contact between cells. Examples: immune cell interactions, embryonic development (Notch pathway), gap junctions (ions and small molecules pass directly between cells)
Cells release signaling molecules into the extracellular fluid that affect nearby target cells. The signal acts locally over a short distance. Examples: growth factors during development, neurotransmitter diffusion across synapses. Requires no direct cell-cell contact
Specialized cells release hormones into the bloodstream for distribution throughout the body. Hormones reach all cells but only target cells with appropriate receptors. Slower response than paracrine but covers long distances. Examples: insulin, adrenaline, estrogen, testosterone
Cells secrete signaling molecules that bind to receptors on the same cell. The cell signals itself. Important in immune responses (immune cells stimulate themselves), development, and cancer (cancer cells secrete growth factors that stimulate their own proliferation)
The first stage of cell signaling. A signal molecule (ligand) binds to a specific receptor protein on or in the target cell. Receptors are specific - each receptor binds only its specific ligand. Three receptor types: cell-surface (hydrophilic ligands), intracellular/cytoplasmic (lipid-soluble ligands: steroids, thyroid hormone)
The second stage. The signal is converted and relayed inside the cell, often through a cascade of reactions. Relay molecules (second messengers, kinases) amplify the signal at each step. One hormone/receptor can activate many downstream molecules -> signal amplification. Examples: G-proteins, phosphorylation cascades, cAMP
The third stage. The transduced signal finally triggers a specific cellular response. Responses can be: enzyme activation/inhibition, gene expression changes (altering transcription), ion channel opening/closing, cytoskeleton rearrangement, cell division initiation. The response is proportional to signal strength
A series of enzyme activations where each step adds a phosphate group to the next enzyme (kinase). Kinases phosphorylate target proteins, changing their activity. One activated kinase can phosphorylate many substrates -> massive signal amplification. The cascade: signal -> receptor -> G-protein -> kinase 1 -> kinase 2 -> kinase 3 -> cellular response
(GPCRs)**: The largest family of cell surface receptors. When a ligand binds: receptor changes shape -> activates a G-protein (GDP -> GTP) -> G-protein subunit activates effector protein (e.g., adenylyl cyclase) -> produces second messenger (cAMP). G-proteins are switched off by hydrolysis of GTP to GDP. ~50% of drugs target GPCRs
Small, non-protein signaling molecules produced inside the cell in response to extracellular signals. cAMP is produced from ATP by adenylyl cyclase (activated by G-proteins). cAMP activates Protein Kinase A (PKA), which phosphorylates target proteins. Quickly broken down by phosphodiesterase. Other second messengers: IP3, DAG, Ca2+, nitric oxide (NO)
Mutations can cause: receptor hyperactivation (constitutively active -> cancer), receptor loss (no signal received), altered ligand binding (cannot receive signal). Mutations in receptor tyrosine kinases (RTKs) are common in cancers (e.g., HER2 in breast cancer)
Molecules that block signal transduction at various points. Competitive inhibitors block ligand binding at receptors. Allosteric inhibitors bind elsewhere, changing receptor shape. Kinase inhibitors block phosphorylation cascades (e.g., imatinib for chronic myelogenous leukemia). Important in pharmacology and cellular regulation
A response that counteracts the original stimulus, maintaining homeostasis. The product of a pathway inhibits an earlier step. Examples: enzyme inhibition by end-product, blood glucose regulation (insulin -> cells take up glucose -> blood glucose falls -> stops insulin secretion), thermostat. Prevents overproduction and maintains stability
A response that amplifies the original stimulus. The product of a pathway activates an earlier step. Examples: childbirth (oxytocin -> contractions -> more oxytocin), blood clotting (clot activates clotting factors -> more clotting), egg activation by sperm. Less common than negative feedback; usually involves a threshold trigger
The maintenance of a stable internal environment despite external changes. Achieved through negative feedback loops. Examples: body temperature, blood glucose, pH, ion concentrations. Disruption of homeostasis leads to disease (e.g., diabetes, fever). Cells respond to environmental changes through signal transduction
A non-dividing state. Cells in G0 may be: temporarily arrested (can re-enter G1), terminally differentiated (never divide again, e.g., nerve cells, muscle cells), or senescent (damaged cells that cannot divide). Regulated by growth factors, cell density, and DNA damage checkpoints
The longest phase of the cell cycle (~90% of the time). G1: cell growth, protein synthesis, organelle duplication. S: DNA replication (chromosomes are duplicated). G2: final growth, preparation for mitosis, checkpoint verification of DNA replication. Cells in G0 (quiescent) do not divide
PMAT - Prophase (chromatin condenses into visible chromosomes, nuclear envelope breaks down, spindle forms), Metaphase (chromosomes align at the metaphase plate, spindle fibers attach to kinetochores), Anaphase (sister chromatids separate and move to opposite poles), Telophase (nuclear envelopes reform, chromosomes decondense, spindle breaks down)
The physical division of the cytoplasm, producing two daughter cells. In animal cells: a cleavage furrow (actin-myosin ring) pinches the cell in two. In plant cells: a cell plate (vesicle fusion) forms in the middle, developing into a new cell wall. Typically overlaps with telophase
Control points where the cell cycle can be halted until conditions are favorable. G1 checkpoint (main decision point): checks cell size, nutrients, DNA damage, growth factor availability. G2 checkpoint: verifies DNA replication is complete and damage-free. M checkpoint (spindle assembly): ensures all chromosomes are properly attached before anaphase begins
Regulatory proteins whose levels rise and fall with each cell cycle. Cyclin concentrations trigger transitions between phases. Cyclin-CDK complexes are the "engine" of the cell cycle. Different cyclins act at different phases: cyclin D/E at G1/S, cyclin A at S/G2, cyclin B at G2/M
Kinase enzymes that are active only when bound to their cyclin partner. Phosphorylate target proteins to drive cell cycle transitions. CDK activity is also regulated by: inhibitory phosphorylation, CDK inhibitors (CKIs), phosphatases. MPF (Maturation Promoting Factor) = cyclin B + CDK1 = drives G2 -> M transition
Programmed cell death - orderly, controlled cell suicide. Triggered by: internal signals (DNA damage -> p53), external signals (death ligands). Steps: cell shrinks, chromatin condenses, blebbing, phagocytosis by macrophages. Prevents cancer, removes damaged cells, shapes tissues during development. Distinct from necrosis (uncontrolled cell death from injury)
Cancer = uncontrolled cell division (loss of cell cycle regulation). Caused by mutations in: proto-oncogenes ( -> oncogenes, gain of function: excessive division signals) and tumor suppressor genes (loss of function: cannot restrain division). Examples: p53 (G1 checkpoint), Rb (E2F inhibitor), HER2, Ras, BRCA. Benign vs malignant (invasive/metastatic) tumors
Direct cell-to-cell contact signaling. A membrane-bound signal on one cell binds to a receptor on an adjacent cell. Requires physical contact between cells. Examples: immune cell interactions, embryonic development (Notch pathway), gap junctions (ions and small molecules pass directly between cells)
Cells release signaling molecules into the extracellular fluid that affect nearby target cells. The signal acts locally over a short distance. Examples: growth factors during development, neurotransmitter diffusion across synapses. Requires no direct cell-cell contact
Specialized cells release hormones into the bloodstream for distribution throughout the body. Hormones reach all cells but only target cells with appropriate receptors. Slower response than paracrine but covers long distances. Examples: insulin, adrenaline, estrogen, testosterone
Cells secrete signaling molecules that bind to receptors on the same cell. The cell signals itself. Important in immune responses (immune cells stimulate themselves), development, and cancer (cancer cells secrete growth factors that stimulate their own proliferation)
The first stage of cell signaling. A signal molecule (ligand) binds to a specific receptor protein on or in the target cell. Receptors are specific - each receptor binds only its specific ligand. Three receptor types: cell-surface (hydrophilic ligands), intracellular/cytoplasmic (lipid-soluble ligands: steroids, thyroid hormone)
The second stage. The signal is converted and relayed inside the cell, often through a cascade of reactions. Relay molecules (second messengers, kinases) amplify the signal at each step. One hormone/receptor can activate many downstream molecules -> signal amplification. Examples: G-proteins, phosphorylation cascades, cAMP
The third stage. The transduced signal finally triggers a specific cellular response. Responses can be: enzyme activation/inhibition, gene expression changes (altering transcription), ion channel opening/closing, cytoskeleton rearrangement, cell division initiation. The response is proportional to signal strength
A series of enzyme activations where each step adds a phosphate group to the next enzyme (kinase). Kinases phosphorylate target proteins, changing their activity. One activated kinase can phosphorylate many substrates -> massive signal amplification. The cascade: signal -> receptor -> G-protein -> kinase 1 -> kinase 2 -> kinase 3 -> cellular response
(GPCRs)**: The largest family of cell surface receptors. When a ligand binds: receptor changes shape -> activates a G-protein (GDP -> GTP) -> G-protein subunit activates effector protein (e.g., adenylyl cyclase) -> produces second messenger (cAMP). G-proteins are switched off by hydrolysis of GTP to GDP. ~50% of drugs target GPCRs
Small, non-protein signaling molecules produced inside the cell in response to extracellular signals. cAMP is produced from ATP by adenylyl cyclase (activated by G-proteins). cAMP activates Protein Kinase A (PKA), which phosphorylates target proteins. Quickly broken down by phosphodiesterase. Other second messengers: IP3, DAG, Ca2+, nitric oxide (NO)
Mutations can cause: receptor hyperactivation (constitutively active -> cancer), receptor loss (no signal received), altered ligand binding (cannot receive signal). Mutations in receptor tyrosine kinases (RTKs) are common in cancers (e.g., HER2 in breast cancer)
Molecules that block signal transduction at various points. Competitive inhibitors block ligand binding at receptors. Allosteric inhibitors bind elsewhere, changing receptor shape. Kinase inhibitors block phosphorylation cascades (e.g., imatinib for chronic myelogenous leukemia). Important in pharmacology and cellular regulation
A response that counteracts the original stimulus, maintaining homeostasis. The product of a pathway inhibits an earlier step. Examples: enzyme inhibition by end-product, blood glucose regulation (insulin -> cells take up glucose -> blood glucose falls -> stops insulin secretion), thermostat. Prevents overproduction and maintains stability
A response that amplifies the original stimulus. The product of a pathway activates an earlier step. Examples: childbirth (oxytocin -> contractions -> more oxytocin), blood clotting (clot activates clotting factors -> more clotting), egg activation by sperm. Less common than negative feedback; usually involves a threshold trigger
The maintenance of a stable internal environment despite external changes. Achieved through negative feedback loops. Examples: body temperature, blood glucose, pH, ion concentrations. Disruption of homeostasis leads to disease (e.g., diabetes, fever). Cells respond to environmental changes through signal transduction
A non-dividing state. Cells in G0 may be: temporarily arrested (can re-enter G1), terminally differentiated (never divide again, e.g., nerve cells, muscle cells), or senescent (damaged cells that cannot divide). Regulated by growth factors, cell density, and DNA damage checkpoints
The longest phase of the cell cycle (~90% of the time). G1: cell growth, protein synthesis, organelle duplication. S: DNA replication (chromosomes are duplicated). G2: final growth, preparation for mitosis, checkpoint verification of DNA replication. Cells in G0 (quiescent) do not divide
PMAT - Prophase (chromatin condenses into visible chromosomes, nuclear envelope breaks down, spindle forms), Metaphase (chromosomes align at the metaphase plate, spindle fibers attach to kinetochores), Anaphase (sister chromatids separate and move to opposite poles), Telophase (nuclear envelopes reform, chromosomes decondense, spindle breaks down)
The physical division of the cytoplasm, producing two daughter cells. In animal cells: a cleavage furrow (actin-myosin ring) pinches the cell in two. In plant cells: a cell plate (vesicle fusion) forms in the middle, developing into a new cell wall. Typically overlaps with telophase
Control points where the cell cycle can be halted until conditions are favorable. G1 checkpoint (main decision point): checks cell size, nutrients, DNA damage, growth factor availability. G2 checkpoint: verifies DNA replication is complete and damage-free. M checkpoint (spindle assembly): ensures all chromosomes are properly attached before anaphase begins
Regulatory proteins whose levels rise and fall with each cell cycle. Cyclin concentrations trigger transitions between phases. Cyclin-CDK complexes are the "engine" of the cell cycle. Different cyclins act at different phases: cyclin D/E at G1/S, cyclin A at S/G2, cyclin B at G2/M
Kinase enzymes that are active only when bound to their cyclin partner. Phosphorylate target proteins to drive cell cycle transitions. CDK activity is also regulated by: inhibitory phosphorylation, CDK inhibitors (CKIs), phosphatases. MPF (Maturation Promoting Factor) = cyclin B + CDK1 = drives G2 -> M transition
Programmed cell death - orderly, controlled cell suicide. Triggered by: internal signals (DNA damage -> p53), external signals (death ligands). Steps: cell shrinks, chromatin condenses, blebbing, phagocytosis by macrophages. Prevents cancer, removes damaged cells, shapes tissues during development. Distinct from necrosis (uncontrolled cell death from injury)
Cancer = uncontrolled cell division (loss of cell cycle regulation). Caused by mutations in: proto-oncogenes ( -> oncogenes, gain of function: excessive division signals) and tumor suppressor genes (loss of function: cannot restrain division). Examples: p53 (G1 checkpoint), Rb (E2F inhibitor), HER2, Ras, BRCA. Benign vs malignant (invasive/metastatic) tumors